Suspected severe malaria in a sudanese patient affected by sickle cell disease who was treated with hydroxyurea

Sickle cell disease (SCD) is the most common genetic disease in sub-Saharan Africa. The signs and symptoms of SCD usually begin in early childhood. Characteristic features of this disorder include anaemia, repeated infections, and periodic episodes of pain. Malaria is one of the infections that can occur in patients with SCD in endemic countries. Many guidelines recommend antimalarial chemoprophylaxis in these patients, although the debate on which drug should be used is still ongoing. Hydroxyurea (HU), which is considered a safe and effective treatment for both children and adults with SCD, seems to affect the incidence and severity of malaria, although these impacts have yet to be fully demonstrated. We report a case of an eight-and-a-half-year-old Sudanese boy with SCD treated with HU admitted for suspected severe malaria who showed a recrudescence after first-line treatment. Although he had undergone splenectomy and thus belonged to a category of patients at high risk for infectious complications, he was not receiving any malaria chemoprophylaxis. This case emphasises the importance of the routine administration of malaria prophylaxis to children with SCD living in endemic areas, even when they are treated with HU, and especially if they are at high risk for infectious complications because they have undergone splenectomy. There is an urgent need for further research to evaluate the most appropriate regimen and its optimal duration

Effect of Long-Term Agricultural Management on the Soil Microbiota Influenced by the Time of Soil Sampling

Application of agrochemicals and mechanization enabled increasing agriculturalproductivity yet caused various environmental and soil health-related problems.Agricultural practices affect soil microorganisms, which are the key players of manyecosystem processes. However, less is known about whether this effect differs betweentime points. Therefore, soil was sampled in winter (without crop) and in summer (inthe presence of maize) from a long-term field experiment (LTE) in Bernburg (Germany)managed either under cultivator tillage (CT) or moldboard plow (MP) in combinationwith either intensive nitrogen (N)-fertilization and pesticides (Int) or extensive reducedN-fertilization without fungicides (Ext), respectively. High-throughput sequencing of 16SrRNA gene and fungal ITS2 amplicons showed that changes in the microbial communitycomposition were correlated to differences in soil chemical properties caused by tillagepractice. Microbial communities of soils sampled in winter differed only depending onthe tillage practice while, in summer, also a strong effect of the fertilization intensity wasobserved. A small proportion of microbial taxa was shared between soils from the twosampling times, suggesting the existence of a stable core microbiota at the LTE. Ingeneral, taxa associated with organic matter decomposition (such as Actinobacteria,Bacteroidetes, Rhizopus, and Exophiala) had a higher relative abundance under CT.Among the taxa with significant changes in relative abundances due to different long-termagricultural practices were putative pathogenic (e.g., Gibellulopsis and Gibberella) andbeneficial microbial genera (e.g., Chitinophagaceae, Ferruginibacter, and Minimedusa).In summary, this study suggests that the effects of long-term agricultural managementpractices on the soil microbiota are influenced by the soil sampling time, and this needsto be kept in mind in future studies for the interpretation of field data.Fil: Fernandez Gnecco, Gabriela Amancay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Covacevich, Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Consolo, Verónica Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Biodiversidad y Biotecnología; ArgentinaFil: Behr, Jan H.. Leibniz Institute Of Vegetable And Ornamental Crops (; AlemaniaFil: Sommermann, Loreen. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Moradtalab, Narges. Department Of Nutritional Crop Physiology, Institute Of; AlemaniaFil: Maccario, Lorrie. Section Of Microbiology, Department Of Biology, Univers; AlemaniaFil: Sørensen, Søren J.. Section Of Microbiology, Department Of Biology, Univers; AlemaniaFil: Deubel, Annette. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Schellenberg, Ingo. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Geistlinger, Joerg. Department Of Agriculture, Ecotrophology And Landscape; AlemaniaFil: Neumann, Günter. Department Of Nutritional Crop Physiology, Institute Of; AlemaniaFil: Grosch, Rita. Leibniz Institute Of Vegetable And Ornamental Crops (; AlemaniaFil: Smalla, Kornelia. Julius Kühn Institut Braunschweig; AlemaniaFil: Babin, Doreen. Julius Kühn Institut Braunschweig; Alemani

Adventage of mesenchymal stem cells (MSC) expansion directly from purified bone marrow CD105^+ and CD271^+ cells

Mesenchymal Stem Cells (MSC) are employed in gene and cellular therapies. Routinely MSC are isolated from bone marrow mononuclear cells (MNC) by plastic adherence. Here we compared new isolation strategies of bone marrow MSC including immunodepletion of hematopoietic cells and immunomagnetic isolation of CD105+ and CD271+ populations. Four fractions were obtained: MNC MSC, RosetteSep-isolated MSC, CD105+ and CD271+ sorted MSC. We evaluated i) number of CFU-F colonies, ii) cell phenotype, iii) in vitro differentiation of expanded cells and iv) expression of osteo/adipogenesis related genes. Results: Average number of day 9 CFU-F colonies was the highest for CD271 positive fraction. Real-Time PCR analysis revealed expression of RUNX2, PPARgamma and N-cadherin in isolated cells, particularly high in CD271+ cells. Expression of CD105, CD166, CD44, CD73 antigens was comparable for all expanded populations (over 90%). We observed various levels of hematopoietic contamination with the highest numbers of CD45+ cells in MNC-MSC fraction and the lowest in CD105+ and CD271+ fractions. Cells of all the fractions were CD34 antigen negative. Expanded CD105 and CD271 populations showed higher level of RUNX2, osteocalcin, PTHR, leptin, PPARgamma2 and aggrecan1 genes except for alpha1 collagen. After osteogenic differentiation CD105+ and CD271+ populations showed lower expression of RUNX, PPARgamma2 and also lower expression of osteocalcin and PTHR than MNC, with comparable alpha1-collagen expression. Chondrogenic and adipogenic gene expression was higher in MNC. More clonogenic CD105+ and particularly CD271+ cells, which seem to be the most homogenous fractions based on Real-Time PCR and immunostaining data, are better suited for MSC expansion

Activation of Regulatory T Cells during Inflammatory Response Is Not an Exclusive Property of Stem Cells

BACKGROUND: Sepsis and systemic-inflammatory-response-syndrome (SIRS) remain major causes for fatalities on intensive care units despite up-to-date therapy. It is well accepted that stem cells have immunomodulatory properties during inflammation and sepsis, including the activation of regulatory T cells and the attenuation of distant organ damage. Evidence from recent work suggests that these properties may not be exclusively attributed to stem cells. This study was designed to evaluate the immunomodulatory potency of cellular treatment during acute inflammation in a model of sublethal endotoxemia and to investigate the hypothesis that immunomodulations by cellular treatment during inflammatory response is not stem cell specific. METHODOLOGY/PRINCIPAL FINDINGS: Endotoxemia was induced via intra-peritoneal injection of lipopolysaccharide (LPS) in wild type mice (C3H/HeN). Mice were treated with either vital or homogenized amniotic fluid stem cells (AFS) and sacrificed for specimen collection 24 h after LPS injection. Endpoints were plasma cytokine levels (BD™ Cytometric Bead Arrays), T cell subpopulations (flow-cytometry) and pulmonary neutrophil influx (immunohistochemistry). To define stem cell specific effects, treatment with either vital or homogenized human-embryonic-kidney-cells (HEK) was investigated in a second subset of experiments. Mice treated with homogenized AFS cells showed significantly increased percentages of regulatory T cells and Interleukin-2 as well as decreased amounts of pulmonary neutrophils compared to saline-treated controls. These results could be reproduced in mice treated with vital HEK cells. No further differences were observed between plasma cytokine levels of endotoxemic mice. CONCLUSIONS/SIGNIFICANCE: The results revealed that both AFS and HEK cells modulate cellular immune response and distant organ damage during sublethal endotoxemia. The observed effects support the hypothesis, that immunomodulations are not exclusive attributes of stem cells

Human predecidual stromal cells are mesenchymal stromal/stem cells and have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion

Human decidual stromal cells (DSCs) are involved in the maintenance and development of pregnancy, in which they play a key role in the induction of immunological maternal–fetal tolerance. Precursors of DSCs (preDSCs) are located around the vessels, and based on their antigen phenotype, previous studies suggested a relationship between preDSCs and mesenchymal stromal/stem cells (MSCs). This work aimed to further elucidate the MSC characteristics of preDSCs. Under the effect of P4 and cAMP, the preDSC lines and clones decidualized in vitro: the cells became rounder and secreted PRL, a marker of physiological decidualization. PreDSC lines and clones also exhibited MSC characteristics. They differentiated into adipocytes, osteoblasts, and chondrocytes, and preDSC lines expressed stem cell markers OCT- 4, NANOG, and ABCG2; exhibited a cloning efficiency of 4 to 15%; significantly reduced the embryo resorption rate (P < 0.001) in the mouse model of abortion; and survived for prolonged periods in immunocompetent mice. The fact that 3 preDSC clones underwent both decidualization and mesenchymal differentiation shows that the same type of cell exhibited both DSC and MSC characteristics. Together, our results confirm that preDSCs are decidual MSCs and suggest that these cells are involved in the mechanisms of maternal–fetal immune toleranceThis work was supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, the Ministerio de Economía y Competitividad, Spain (Grant PI16/01642) and European Regional Development Fund (ERDF/ FEDER funding), the European Community, and the Cátedra de Investigación Anto nio Chamorro–Alejandro Otero, Universidad de Granada (CACH2017-1)

Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7