We analyzed the metabolic activity of Shewanella oneidensis MR-1 respiring on an indium tin-doped oxide electrode with nanoscale secondary ion mass spectrometry (NanoSIMS) for quantification of the anabolism of 15 N-labeled NH 4 Cl. Although acceleration of extracellular electron transfer (EET) did not enhance the average metabolic activity, the distribution of 15 N intake among individual cells was drastically bipolarized upon EET rate enhancement, suggesting not only positive but also negative effects on cellular activity. The present data highlight the importance of controlling the downregulation of metabolic activity caused by the rate acceleration of EET to improve the efficiency of microbial electrode catalysis.
Summary:We describe a patient who developed unilateral papilledema after allogeneic BMT. This is a rare manifestation of pseudotumor cerebri, which results from elevated intracranial pressure caused by cyclosporin A. The papilledema usually involves the fundi bilaterally, but unilateral involvement has been described. Congenital anomalies, compression and adhesion of the optic nerve sheath are its causes. In this patient, the right optic fundus was spared although leukemic infiltration was present on this side and high-dose irradiation (72 Gy) was given. Although papilledema is a sensitive marker of elevated intracranial pressure, this sign may be masked by constriction of the optic sheath in patients who suffer from leukemic infiltration of the central nervous system and receive high doses of cranial irradiation. Keywords: unilateral papilledema; pseudotumor cerebri; cyclosporine Ocular complications after BMT have been well described. Acute and chronic graft-versus-host disease (GVHD), conditioning therapy, prophylaxis and treatment of GVHD (corticosteroids and cyclosporin A) and a variety of infections may cause the ophthalmologic problems.The adverse ophthalmologic effects of cyclosporin A (CsA) are frequently reported. These include cortical blindness, 1 microvascular retinopathy, 2 ocular flutter 3 and pseudotumor cerebri. 4 Because they potentially progress to cause life-threatening central nervous system (CNS) complications CsA must be discontinued in some cases.Papilledema is a sign of elevated intracranial pressure. Infection and infiltration by malignant cells in the CNS are the chief causes of this complication. Sometimes, patients who have no definite signs of intracranial problems develop papilledema, which usually involves the fundi bilaterally. These are diagnosed as pseudotumor cerebri. However, unilateral involvement has also been reported, 5,6 but the exact pathomechanism is unknown. Here, we report a patient who Correspondence: Dr Y Fujino, Department of Ophthalmology, Tokyo University Branch Hospital, University of Tokyo, 3-28-6, Mejirodai, Bunkyoku, Tokyo 112-8688, Japan Received 24 August 1998; accepted 3 December 1998 developed unilateral papilledema after allogeneic BMT. This is the first report of this rare ocular complication after BMT. Case reportIn July 1996, a 26-year-old male with t(8;21) positive acute myeloid leukemia in second relapse was transferred to our hospital for allogeneic BMT. He had received 40 Gy of whole brain irradiation for the leukemic infiltration in the CNS and an additional 20 Gy for residual leukemia in the right mastoid sinus. We succeeded in controlling the CNS lesions with the radiotherapy and intrathecal MTX. No abnormalities were noted on the pre-transplant ophthalmologic examination.He underwent an allogeneic BMT in August 1996. Conditioning was with G-CSF, cytarabine, MCNU and fractionated TBI. GVHD prophylaxis was the combination of shortterm MTX and cyclosporine.The patient was seen at day 65 after BMT for routine ophthalmologic examination. At that t...
Outer-membrane c-type cytochrome (OM c-Cyt) complexes in several genera of iron-reducing bacteria, such as Shewanella and Geobacter, are capable of transporting electrons from the cell interior to extracellular solids as a terminal step of anaerobic respiration. The kinetics of this electron transport has implications for controlling the rate of microbial electron transport during bioenergy or biochemical production, iron corrosion, and natural mineral cycling. Herein, we review the findings from in-vivo and in-vitro studies examining electron transport kinetics through single OM c-Cyt complexes in Shewanella oneidensis MR-1. In-vitro electron flux via a purified OM c-Cyt complex, comprised of MtrA, B, and C proteins from S. oneidensis MR-1, embedded in a proteoliposome system is reported to be 10- to 100-fold faster compared with in-vivo estimates based on measurements of electron flux per cell and OM c-Cyts density. As the proteoliposome system is estimated to have 10-fold higher cation flux via potassium channels than electrons, we speculate that the slower rate of electron-coupled cation transport across the OM is responsible for the significantly lower electron transport rate that is observed in-vivo. As most studies to date have primarily focused on the energetics or kinetics of interheme electron hopping in OM c-Cyts in this microbial electron transport mechanism, the proposed model involving cation transport provides new insight into the rate detemining step of EET, as well as the role of self-secreted flavin molecules bound to OM c-Cyt and proton management for energy conservation and production in S. oneidensis MR-1.
Early steps of the biosynthetic pathway of the insect steroid hormone ecdysone remains the "Black Box" wherein the characteristic ecdysteroid skeleton is built. 7-Dehydrocholesterol (7dC) is the precursor of uncharacterized intermediates in the Black Box. The oxidation step at C-3 has been hypothesized during conversion from 7dC to 3-oxo-2,22,25-trideoxyecdysone, yet 3-dehydroecdysone is undetectable in some insect species. Therefore, we first confirmed that the oxidation at C-3 occurs in the fruitfly, Drosophila melanogaster using deuterium-labeled cholesterol. We next investigated the molting activities of candidate intermediates, including oxidative products of 7dC, by feeding-rescue experiments for Drosophila larvae in which an expression level of a biosynthetic enzyme was knocked down by the RNAi technique. We found that the administration of cholesta-4,7-dien-3-one (3-oxo-ΔC) could overcome the molting arrest of ecdysteroid-defective larvae in which the expression level of neverland was reduced. However, feeding 3-oxo-ΔC to larvae in which the expression levels of shroud and Cyp6t3 were reduced inhibited molting at the first instar stage, suggesting that this steroid could be converted into an ecdysteroid-antagonist in loss of function studies of these biosynthetic enzymes. Administration of the highly conjugated cholesta-4,6,8(14)-trien-3-one, oxidized from 3-oxo-ΔC, did not trigger molting of ecdysteroid-defective larvae. These results suggest that an oxidative product derived from 7dC is converted into ecdysteroids without the formation of this stable conjugated compound. We further found that the 14α-hydroxyl moiety of Δ-steroids is required to overcome the molting arrest of larvae in loss of function studies of Neverland, Shroud, CYP6T3 or Spookier, suggesting that oxidation at C-14 is indispensable for conversion of these Δ-steroids into ecdysteroids via 5β-reduction.
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