Triple tSMS system ("SHIN jiba") for non-invasive deep brain stimulation: a validation study in healthy subjects.

BACKGROUND: Transcranial static magnetic field stimulation (tSMS) using a small and strong neodymium (NdFeB) magnet can temporarily suppress brain functions below the magnet. It is a promising non-invasive brain stimulation modality because of its competitive advantages such as safety, simplicity, and low-cost. However, current tSMS is insufficient to effectively stimulate deep brain areas due to attenuation of the magnetic field with the distance from the magnet. The aim of this study was to develop a brand-new tSMS system for non-invasive deep brain stimulation. METHODS: We designed and fabricated a triple tSMS system with three cylindrical NdFeB magnets placed close to each other. We compared the strength of magnetic field produced by the triple tSMS system with that by the current tSMS. Furthermore, to confirm its function, we stimulated the primary motor area in 17 healthy subjects with the triple tSMS for 20 min and assessed the cortical excitability using the motor evoked potential (MEP) obtained by transcranial magnetic stimulation. RESULTS: Our triple tSMS system produced the magnetic field sufficient for neuromodulation up to 80 mm depth from the magnet surface, which was 30 mm deeper than the current tSMS system. In the stimulation experiment, the triple tSMS significantly reduced the MEP amplitude, demonstrating a successful inhibition of the M1 excitability in healthy subjects. CONCLUSION: Our triple tSMS system has an ability to produce an effective magnetic field in deep areas and to modulate the brain functions. It can be used for non-invasive deep brain stimulation.

A Deafness- and Diabetes-associated tRNA Mutation Causes Deficient Pseudouridinylation at Position 55 in tRNAGlu and Mitochondrial Dysfunction.

Several mitochondrial tRNA mutations have been associated with maternally inherited diabetes and deafness. However, the pathophysiology of these tRNA mutations remains poorly understood. In this report, we identified the novel homoplasmic 14692A→G mutation in the mitochondrial tRNAGlu gene among three Han Chinese families with maternally inherited diabetes and deafness. The m.14692A→G mutation affected a highly conserved uridine at position 55 of the TΨC loop of tRNAGlu The uridine is modified to pseudouridine (Ψ55), which plays an important role in the structure and function of this tRNA. Using lymphoblastoid cell lines derived from a Chinese family, we demonstrated that the m.14692A→G mutation caused loss of Ψ55 modification and increased angiogenin-mediated endonucleolytic cleavage in mutant tRNAGlu The destabilization of base-pairing (18A-Ψ55) caused by the m.14692A→G mutation perturbed the conformation and stability of tRNAGlu An approximately 65% decrease in the steady-state level of tRNAGlu was observed in mutant cells compared with control cells. A failure in tRNAGlu metabolism impaired mitochondrial translation, especially for polypeptides with a high proportion of glutamic acid codons such as ND1, ND6, and CO2 in mutant cells. An impairment of mitochondrial translation caused defective respiratory capacity, especially reducing the activities of complexes I and IV. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These mitochondrial dysfunctions caused an increasing production of reactive oxygen species in the mutant cells. Our findings may provide new insights into the pathophysiology of maternally inherited diabetes and deafness, which is primarily manifested by the deficient nucleotide modification of mitochondrial tRNAGlu.

Roles of alkyl hydroperoxide reductase subunit C (AhpC) in viable but nonculturable Vibrio parahaemolyticus.

Alkyl hydroperoxide reductase subunit C (AhpC) is the catalytic subunit responsible for the detoxification of reactive oxygen species that form in bacterial cells or are derived from the host; thus, AhpC facilitates the survival of pathogenic bacteria under environmental stresses or during infection. This study investigates the role of AhpC in the induction and maintenance of a viable but nonculturable (VBNC) state in Vibrio parahaemolyticus. In this investigation, ahpC1 (VPA1683) and ahpC2 (VP0580) were identified in chromosomes II and I of this pathogen, respectively. Mutants with deletions of these two ahpC genes and their complementary strains were constructed from the parent strain KX-V231. The growth of these strains was monitored on tryptic soy agar-3% NaCl in the presence of the extrinsic peroxides H(2)O(2) and tert-butyl hydroperoxide (t-BOOH) at different incubation temperatures. The results revealed that both ahpC genes were protective against t-BOOH, while ahpC1 was protective against H(2)O(2). The protective function of ahpC2 at 4°C was higher than that of ahpC1. The times required to induce the VBNC state (4.7 weeks) at 4°C in a modified Morita mineral salt solution with 0.5% NaCl and then to maintain the VBNC state (4.7 weeks) in an ahpC2 mutant and an ahpC1 ahpC2 double mutant were significantly shorter than those for the parent strain (for induction, 6.2 weeks; for maintenance, 7.8 weeks) and the ahpC1 mutant (for induction, 6.0 weeks; for maintenance, 8.0 weeks) (P < 0.03). Complementation with an ahpC2 gene reversed the effects of the ahpC2 mutation in shortening the times for induction and maintenance of the VBNC state. This investigation identified the different functions of the two ahpC genes and confirmed the particular role of ahpC2 in the VBNC state of V. parahaemolyticus.

Frontiers of parasitology research in the People's Republic of China: infection, diagnosis, protection and surveillance.

Control and eventual elimination of human parasitic diseases in the People's Republic of China (P.R. China) requires novel approaches, particularly in the areas of diagnostics, mathematical modelling, monitoring, evaluation, surveillance and public health response. A comprehensive effort, involving the collaboration of 188 scientists (>85% from P.R. China) from 48 different institutions and universities (80% from P.R. China), covers this collection of 29 articles published in Parasites & Vectors. The research mainly stems from a research project entitled "Surveillance and diagnostic tools for major parasitic diseases in P.R. China" (grant no. 2008ZX10004-011) and highlights the frontiers of research in parasitology. The majority of articles in this thematic series deals with the most important parasitic diseases in P.R. China, emphasizing Schistosoma japonicum, Plasmodium vivax and Clonorchis sinensis plus some parasites of emerging importance such as Angiostrongylus cantonensis. Significant achievements have been made through the collaborative research programme in the following three fields: (i) development of strategies for the national control programme; (ii) updating the surveillance data of parasitic infections both in human and animals; and (iii) improvement of existing, and development of novel, diagnostic tools to detect parasitic infections. The progress is considerable and warrants broad validation efforts. Combined with the development of improved tools for diagnosis and surveillance, integrated and multi-pronged control strategies should now pave the way for elimination of parasitic diseases in P.R. China. Experiences and lessons learned can stimulate control and elimination efforts of parasitic diseases in other parts of the world.

[Correlation of bone marrow stromal function in vitro with efficacy of anisodamine therapy for aplastic anemia].

To observe normal bone marrow stromal function for supporting hematopoiesis and realize the correlation of bone marrow stromal function in patients with aplastic anemia (AA) and anisodamine therapy, normal human marrow CFU-GM was assayed on bone marrow stromal layer (SL) formed on week 3 culture, and the CFU-GM without SL as a control (100%). Results showed that the production of CFU-GM on the normal SL was significantly higher than that of the control. The production of CFU-GM on the SL of 4 AA patients, who responded to anisodamine, was < 80% of the control, and when 2 of them were reexamined for stromal function after treatment, the number of CFU-GM on SL rose up to 168.8% and 249.2% from 38.7% and 39.7% of the control respectively. While in the rest 6 patients, the number of CFU-GM was > 80% of the control, only one patient was improved by anisodamine therapy. So, normal bone marrow stromal layer can obviously support the growth of granulocyte/macrophage progenitor cells. Anisodamine therapy could be an effective agents for aplastic anemia with stromal dysfunction