Diagnosis and molecular basis of mitochondrial respiratory chain disorders: exome sequencing for disease gene identification.

Mitochondrial disorders have the highest incidence among congenital metabolic diseases, and are thought to occur at a rate of 1 in 5000 births. About 25% of the diseases diagnosed as mitochondrial disorders in the field of pediatrics have mitochondrial DNA abnormalities, while the rest occur due to defects in genes encoded in the nucleus. The most important function of the mitochondria is biosynthesis of ATP. Mitochondrial disorders are nearly synonymous with mitochondrial respiratory chain disorder, as respiratory chain complexes serve a central role in ATP biosynthesis. By next-generation sequencing of the exome, we analyzed 104 patients with mitochondrial respiratory chain disorders. The results of analysis to date were 18 patients with novel variants in genes previously reported to be disease-causing, and 27 patients with mutations in genes suggested to be associated in some way with mitochondria, and it is likely that they are new disease-causing genes in mitochondrial disorders. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

Modification of transformer coupled permeameter for frequency extension.

A broadband and high-sensitivity permeability measurement system that covers 10 MHz-20 GHz was previously developed and named the transformer coupled permeameter (TC-Perm). This paper describes the modifications of the TC-Perm system to further extend the operation frequency range on both the high and low frequency sides. In the previous system, the high frequency limit was set by a large notch appearing at around 22 GHz, which was considered to be caused by the excitation of two unwanted modes. In the new system, the jig design was modified to have a back ground plane and vias to suppress these unwanted modes, which resulted in a clean transmission characteristic over the entire frequency range up to 44 GHz. The low frequency limit is determined by the noise figure (NF) of the vector network analyzer input, which was measured to be ∼35 dB in the previous system configuration. The new system employed a low noise amplifier and analog switches to improve the NF to be 2.7 dB below 100 MHz. As a result of these modifications, the operation frequency range of the new TC-Perm system was extended to cover 1 MHz-44 GHz, which is sufficient for characterizing magnetic materials used in noise suppression sheets targeting fifth-generation millimeter-wave (5G mmWave) wireless communication.

Vector network analyzer ferromagnetic resonance spectrometer with field differential detection.

This work presents a vector network analyzer ferromagnetic resonance (VNA-FMR) spectrometer with field differential detection. This technique differentiates the S-parameter by applying a small binary modulation field in addition to the DC bias field to the sample. By setting the modulation frequency sufficiently high, slow sensitivity fluctuations of the VNA, i.e., low-frequency components of the trace noise, which limit the signal-to-noise ratio of the conventional VNA-FMR spectrometer, can be effectively removed, resulting in a very clean FMR signal. This paper presents the details of the hardware implementation and measurement sequence as well as the data processing and analysis algorithms tailored for the FMR spectrum obtained with this technique. Because the VNA measures a complex S-parameter, it is possible to estimate the Gilbert damping parameter from the slope of the phase variation of the S-parameter with respect to the bias field. We show that this algorithm is more robust against noise than the conventional algorithm based on the linewidth.

Prognosis of HTLV-I-positive renal transplant recipients.

HTLV-I is the pathogen that causes adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). The rate of disease development is low and the latency time is a few decades. However, the possible influence of immunosuppression on this disease development is unclear. The purpose of this study was to investigate the risk of development of ATL and HAM among the large number of HTLV-I-positive renal transplant recipients in western Japan. In principle immunosuppressive drugs have the possibilities to accelerate ATL development but are thought to suppress HAM development. Of 120 renal transplant recipients, 10 HTLV-I-positive recipients were reviewed, none of whom developed ATL or HAM. There are 11,896 dialysis patients in Japan and 300 dialysis patients in Okinawa who are registered with the JOTN for cadaveric renal transplant. The numbers of HTLV-I-positive patients in these groups were 97 (0.82%) and 26 (8.67%), respectively. These numbers are thought to be sufficient for an HTLV-I-positive recipient pool for HTLV-I-positive donors. Ten cases of ATL development and two of HAM development have been previously reported. Because of low number of ATL development, renal transplantation does not appear to be a contraindication for HTLV-I-positive chronic renal failure patients. In other words, kidneys from HTLV-I carriers, which include cadaveric donors, could be used for HTLV-I-positive recipients.

Rational design of a sugar-appended porphyrin gelator that is forced to assemble into a one-dimensional aggregate.

[structure--see text] As an attempt to rationally design organogelators, an amphiphilic porphyrin bearing four beta-D-galactopyranoside groups at its periphery was synthesized. This compound tends to aggregate in a one-dimensional direction, resulting in very robust gels in DMF/alcohol mixed solvents. Spectroscopic studies and electron-micrographic observations support the view that the pi-pi stacking interaction among porphyrin moieties and the hydrogen-bonding interaction among sugar moieties operate synergistically to give rise to a stable one-dimensional aggregate structure indispensable for gel formation.

Measurement of ultra-low power oscillators using adaptive drift cancellation with applications to nano-magnetic spin torque oscillators.

This work presents a technique for measuring ultra-low power oscillator signals using an adaptive drift cancellation method. We demonstrate this technique through spectrum measurements of a sub-pW nano-magnet spin torque oscillator (STO). We first present a detailed noise analysis of the standard STO characterization apparatus to estimate the background noise level, then compare these results to the noise level of three measurement configurations. The first and second share the standard configuration but use different spectrum analyzers (SA), an older model and a state-of-the-art model, respectively. The third is the technique proposed in this work using the same old SA as for the first. Our results show that the first and second configurations suffer from a large drift that requires ~30 min to stabilize each time the SA changes the frequency band, even though the SA has been powered on for longer than 24 h. The third configuration introduced in this work, however, shows absolutely no drift as the SA changes frequency band, and nearly the same noise performance as with a state-of-the-art SA, thus providing a reliable method for measuring very low power signals for a wide variety of applications.

[Bathing in bed accelerates the recovery of skin temperature after ethanol-loading].

Bathing in bed (BB) is an essential nursing technique applied to patients with restricted physical abilities. The aim of this technique is to keep the functions of the skin as an external barrier and to prevent the patients from infection and decubitus. However, the effect of BB on the blood circulation of the skin has not yet been identified, and the data observed are controversial. We have evaluated the effects of BB on the blood circulation of the skin by use of thermography. BB was applied on the right side of the back (RB) in 6 healthy female subjects who exposed both sides of their back (RB and LB) at room temperature. Ethanol was applied on the 5 x 5 cm area of RB and LB after BB, and recovery of the skin temperature was observed. After BB, the average temperature of RB was significantly lower than that of LB. This shows that BB decreases temperature of the skin exposed in the air probably due to the supply of water by washcloth. Recovery of the skin temperature after the ethanol-loading was accelerated on RB. This indicates that BB facilitates the response of the blood vessels in the skin.

A hydrogen-bonding receptor that binds cationic monosaccharides with high affinity in methanol.

A dicarboxylate host (1) binds cationic monosaccharides such as D-glucosamine HCl (2), D-galactosamine-HCl (3), and D-mannosamine-HCl (4) with high affinity (K1 = 8.0 x 10(4)-2.0 x 10(5) M(-1)) in methanol. In circular dichroism (CD) spectroscopy a positive exciton-coupling band was observed near 290 nm; this indicates that the saccharides are recognized by multiple point interactions. Since the corresponding neutral monosaccharides are not significantly bound, one may conclude that complex formation is primarily due to the electrostatic interaction between NH3+ in the guest and one carboxylate in the host and secondarily due to hydrogen-bonding interactions of OH groups with the other carboxylate and/or nitrogen bases. Molar ratio plots and Job plots indicate that host 1 and cationic monosaccharide guests form CD-active, pseudo-cyclic 1:1 complexes at low guest concentration followed by the formation of CD-silent, acyclic 1:2 1-saccharide complexes at high guest concentration. The possible binding modes are discussed in detail on the basis of molecular mechanics calculations and chemical shift changes in 1H NMR spectra. The results of competition experiments with several cationic reference compounds bearing fewer OH groups than 2-4 are consistent with the proposed binding model. Thus, the present study is a rare example of saccharide recognition in a protic solvent, where in general, hydrogen-bonding interactions are rarely useful because of strong solvation energy. These are apparently the strongest saccharide complexes involving noncovalent interactions between host and guest. We believe that the findings are significant as a milestone toward development of new saccharide recognition systems ultimately useful in aqueous solution.