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During mixed-acid fermentation, Escherichia coli transports succinate mainly via transporters of the Dcu family. Here, we analyze the influence of Dcu transporters on hydrogenase (Hyd) and fermentative formate dehydrogenase (FDH-H) activities and how this is affected by external pH and carbon source. Using selected dcu mutations, it was shown that Dcu carriers mainly affect Hyd and FDH-H activities during glycerol but not glucose fermentation at acidic pH. During glycerol fermentation at pH 5.5, inactivation of either one or all Dcu carriers increased total Hyd activity by 60% compared with wild type. Under the same growth conditions, a dcuACBD mutant had a twofold higher FDH-H activity. When glucose was fermented in dcuD single mutant at pH 5.5, the FDH-H activity was also increased twofold compared with wild type. Interestingly, in dcuD or dcuACBD mutants at pH 7.5, Hyd activity was lowered by 20%. Taken together, it can be concluded that during glucose fermentation at pH 7.5, lack of DcuD affects Hyd enzyme activity, but at pH 5.5, it has a stronger effect on FDH-H activity. During glycerol fermentation, lack of Dcu carriers increased Hyd and FDH-H activities as revealed at pH 5.5. The results suggest that impairing Dcu transport function increases intracellular formate levels and thus affects H2 cycling and proton-motive force generation. © 2020 International Union of Biochemistry and Molecular Biology.Acute lymphoblastic leukemia (ALL) is often composed of numerous subclones. Here we test whether the clonal composition of the blood is representative of the bone marrow at leukemia onset. Using ultra-deep IGH sequencing, we detected 28 clones across 16 patients; 5/28 were only in the marrow. In four patients, the most abundant clones differed between sites, including three in which the dominant medullary clones were minimally detectable in the blood. These findings demonstrate that the peripheral blood often underrepresents the genetic heterogeneity in a B-ALL and highlight the potential impact of tissue site selection on the detection of minor subclones. © 2020 Wiley Periodicals, Inc.Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are common conditions following motor vehicle accidents (MVAs). Mild TBI and PTSD not only share similar features but may also coexist and interact. Nonetheless, research on psychotherapeutic interventions for PTSD in patients with a history of mTBI, particularly regarding pediatric populations, is limited. The present study compared the efficacy of the prolonged exposure treatment protocol for children and adolescents (PE-A) with PTSD and mTBI (n = 16) versus PTSD alone (n = 21); treatment commenced at least 3 months following an MVA. Emotional status and cognitive functioning were assessed pre- and postintervention using questionnaires and standardized neuropsychological tests. Participants from both groups benefitted from the intervention, as reflected in their emotional status via increased ratings of well-being and decreased ratings of PTSD, anxiety, depression, and postconcussive symptoms, η2 = .21-.50. Ratings of cognitive function also improved for cognitive flexibility, η2 = .30; executive function in everyday life, η2 = .27; and attention and inhibition, η2 = .16. Parental PTSD was the strongest predictor of improvement after intervention, sr2 = .35. Thus, it appears that PE-A is an effective intervention for children with MVA-related PTSD regardless of its comorbidity with mTBI. © 2020 International Society for Traumatic Stress Studies.BACKGROUND Malignant and multicystic peritoneal mesotheliomas are extremely rare tumors in children, developing from mesothelial cells. No specific guidelines are available at this age. METHODS We performed a retrospective analysis of all identified children ( less then 18-year-old) treated in France from 1987 to 2017 for a diffuse malignant peritoneal mesothelioma (DMPM) or a multicystic peritoneal mesothelioma (MCPM). RESULTS Fourteen patients (5 males and nine females), aged 2.2 to 17.5 years, were included. The most frequent presenting symptoms were abdominal pain, ascitis, and alteration in the general condition. Eight patients had epithelioid mesothelioma, three had biphasic mesothelioma, and three had MCPM. Eight patients with DMPM diagnosis received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Among them, six patients had neoadjuvant systemic chemotherapy, one patient, post-operative chemotherapy, and one patient CRS and HIPEC only. Three patients received only systemic chemotherapy. All patients with MCPM had only surgery. learn more After a median follow-up of seven years (2-15), six patients (6/11; one death) with DMPM and two patients (two/three) with MCPM had a local and distant recurrences. CONCLUSION Peritoneal mesothelioma in children is a rare condition with difficult diagnosis and high risk of recurrence. Worldwide interdisciplinary collaboration and networking are mandatory to help diagnosis and provide harmonious treatment guidelines. © 2020 Wiley Periodicals, Inc.BACKGROUND The SRP54 (signal recognition protein 54) is a conserved component of the ribonucleoprotein complex that mediates cotranslational targeting and translocation of proteins to the endoplasmic reticulum. In 2017, mutations in the gene have been described as a cause of congenital neutropenia with or without pancreatic insufficiency, and since then, only limited cases were added to the literature. METHODS Two patients with neutropenia underwent hematological, immunological, and genetic work-up, including lymphocyte phenotyping, immunoglobulins, and complement levels, antineutrophil and antinuclear antibodies, bone marrow FISH panel for myelodysplastic syndrome, whole-exome sequencing, and in silico proteomic analysis. RESULTS Clinical findings in the two families revealed a wide spectrum of immunological and clinical manifestations, ranging from mild asymptomatic neutropenia during febrile illnesses to severe neutropenia and life-threatening infection requiring leg amputation. Immunological and hematological work-up showed isolated neutropenia with normal lymphocyte subpopulations, immunoglobulin and complement levels, and negative autoimmune tests. Bone marrow aspirations showed variability ranging from normal myelopoiesis to myeloid maturation arrest at the promyelocytic stage, with normal FISH panel for myelodysplastic syndrome. Genetic analysis identified a novel, de novo, in-frame deletion in the SRP54 gene, c.342-344delAAC, p.T115del. In silico proteomic analysis suggested impaired SRP54 protein function due to reduced GTP activity and stability. CONCLUSIONS We describe congenital neutropenia with variable clinical presentation in novel mutation of the SRP54 gene. © 2020 Wiley Periodicals, Inc.
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