A Catalytic Role of XoxF1 as La3+-Dependent Methanol Dehydrogenase in Methylobacterium extorquens Strain AM1

In the methylotrophic bacterium Methylobacterium extorquens strain AM1, MxaF, a Ca2+-dependent methanol dehydrogenase (MDH), is the main enzyme catalyzing methanol oxidation during growth on methanol. The genome of strain AM1 contains another MDH gene homologue, xoxF1, whose function in methanol metabolism has remained unclear. In this work, we show that XoxF1 also functions as an MDH and is La3+-dependent. Despite the absence of Ca2+ in the medium strain AM1 was able to grow on methanol in the presence of La3+. Addition of La3+ increased MDH activity but the addition had no effect on mxaF or xoxF1 expression level. We purified MDH from strain AM1 grown on methanol in the presence of La3+, and its N-terminal amino acid sequence corresponded to that of XoxF1. The enzyme contained La3+ as a cofactor. The ΔmxaF mutant strain could not grow on methanol in the presence of Ca2+, but was able to grow after supplementation with La3+. Taken together, these results show that XoxF1 participates in methanol metabolism as a La3+-dependent MDH in strain AM1

Cavernous malformation of the optic chiasm with continuous hemorrhage in a pregnant woman: A case report

Background Cavernous malformation of the anterior visual pathway is rare, especially in pregnant woman. Planning a treatment strategy with cross-disciplinary specialists is important. Case description A 27-year-old pregnant woman presented with acute hemorrhage around the right optic nerve and chiasm, manifesting as poor vision in both eyes. Examination revealed right-eye deteriorated acuity and bilateral temporal hemianopsia. Computed tomography showed an oval high-density mass in the suprasellar region. Gradient echo-based T2-weighted magnetic resonance imaging showed the lesion to be hypointense (possibly a hematoma) and mainly in the optic chiasm. Fluid attenuated inversion recovery imaging showed a bilateral optic tract surrounding the lesion, which enlarged over 1 week, increasing the loss of visual function. Five days after admission, she delivered a healthy >2500-g baby by cesarean section (CS). Right frontotemporal craniotomy was performed 7 days after CS. Incision of the right optic nerve's lateral surface revealed clotted blood with abnormal vascular construction from the right side of the chiasm. We removed the hematoma and vascular lesion. Visual evoked potentials were detected only after optic chiasm decompression. Histological evaluation revealed a hematoma-like lesion with capsules and hemosiderin deposition, suggesting cavernous malformation. Her postoperative recovery was uneventful, with right visual acuity returning to normal, and her visual field not deteriorating any more. Conclusion Devising a treatment strategy with the obstetrician was important in this case to manage the hematoma and cavernous malformation safely

Lanthanide-Dependent Methanol and Formaldehyde Oxidation inMethylobacterium aquaticumStrain 22A

Lanthanides (Ln) are an essential cofactor for XoxF-type methanol dehydrogenases (MDHs) in Gram-negative methylotrophs. The Ln(3+)dependency of XoxF has expanded knowledge and raised new questions in methylotrophy, including the differences in characteristics of XoxF-type MDHs, their regulation, and the methylotrophic metabolism including formaldehyde oxidation. In this study, we genetically identified one set of Ln(3+)- and Ca2+-dependent MDHs (XoxF1 and MxaFI), that are involved in methylotrophy, and an ExaF-type Ln(3+)-dependent ethanol dehydrogenase, among six MDH-like genes inMethylobacterium aquaticumstrain 22A. We also identified the causative mutations in MxbD, a sensor kinase necessary formxaFexpression andxoxF1repression, for suppressive phenotypes inxoxF1mutants defective in methanol growth even in the absence of Ln(3+). Furthermore, we examined the phenotypes of a series of formaldehyde oxidation-pathway mutants (fae1,fae2,mchin the tetrahydromethanopterin (H4MPT) pathway andhgdin the glutathione-dependent formaldehyde dehydrogenase (GSH) pathway). We found that MxaF produces formaldehyde to a toxic level in the absence of the formaldehyde oxidation pathways and that either XoxF1 or ExaF can oxidize formaldehyde to alleviate formaldehyde toxicity in vivo. Furthermore, the GSH pathway has a supportive role for the net formaldehyde oxidation in addition to the H4MPT pathway that has primary importance. Studies on methylotrophy inMethylobacteriumspecies have a long history, and this study provides further insights into genetic and physiological diversity and the differences in methylotrophy within the plant-colonizing methylotrophs

A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children

No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation