Structural analysis of crystalline R(+)-α-lipoic acid-α-cyclodextrin complex based on microscopic and spectroscopic studies

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of 1H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S–S and C–S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring. © 2015 by the authors; licensee MDPI, Basel, Switzerland

RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS

Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone–collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.Shimizu Mikito, Shiraishi Naoyuki, Tada Satoru, et al. RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS. Science Advances 9, 686 (2023); https://doi.org/10.1126/sciadv.adg3193

Usefulness of Combined Electrophysiological Examinations for Detection of Neural Dysfunction in Cats with Lumbar Hematomyelia(Internal Medicine)

金沢大学大学院自然科学研究科 信頼性システム工学交通事故により腰髄出血が生じ, 両後肢麻痺を呈したネコ2症例に対して, F波, 運動神経伝導速度検査(MNCV), 脊髄誘発電位(SCEP)ならびに針筋電図検査(EMG)を実施した.F波, SCEPは事故後3日以内に異常を示した.MNCVおよびEMGは, 事故直後は正常であったが, 6あるいは8日目に異常を示した.複数の電気生理学的検査を繰り返し実施する事により, 神経損傷の進行を推察できることが示唆された. We conducted combined electrophysiological examinations including F-wave, motor nerve conduction velocity (MNCV), spinal cord-evoked potential (SCEP), and needle electromyography (EMG) in two cats involved in traffic accidents that consequently developed hind limb paralysis caused by lumbar hematomyelia. F-wave could no longer be elicited within 3 days after the accident, and the MNCV and compound muscle action potential (CMAP) amplitude decreased in a time-dependent manner, with CMAP no longer being evoked after 7 or 8 days. EMG showed abnormalities such as fibrillation and positive sharp waves after 6 to 8 days. These results suggest that such combined electrophysiological examinations may provide objective, quantitative data for motor nerve dysfunction in cats with lumbar hematomyelia

Effectiveness of intraoperative somatosensory evoked potential monitoring during cervical spinal operations on animals with spinal cord dysfunction

金沢大学大学院自然科学研究科 信頼性システム工学頸髄疾患のイヌ3頭に対して, 頸髄感覚伝導路機能を連続的にモニターする目的で, 尺骨神経刺激による体性感覚誘発電位(SEP)を手術中に測定した.全てのイヌにおいて, 安定したSEPを記録することができた.その頂点間振幅は, 頸髄への施術により減少し, 中断すると回復した.以上の結果より, 頸椎手術において手術操作が脊髄感覚機能へ及ぼす影響を, SEPにより即時的に確認できることが示唆された. We conducted somatosensory evoked potential (SEP) monitoring on 3 dogs with cervical spinal cord dysfunction caused by various diseases throughout operative procedures to examine whether the intraoperative SEP monitoring was effective for prediction of spinal cord conductive function. The SEP was recorded on the scalp via stimulation of the ulnar nerve. Stable SEP was recorded in all animals examined. Its amplitude was decreased by surgical manipulations of the regio vertebralis, but the amplitude gradually recovered once the manipulations were halted. The latency showed small variation throughout the operations. This evidence suggests that intraoperative SEP monitoring may provide continuous and instantaneous information regarding the functional integrity of the central nervous system

Using a mixture of n-best lists from multiple MT systems in rank-sum-based confidence measure for MT outputs

This paper addressees the problem of eliminating unsatisfactory outputs from machine translation (MT) systems. The authors intend to eliminate unsatisfactory MT outputs by using confidence measures. Confidence measures for MT outputs include the rank-sum-based confidence measure (RSCM) for statistical machine translation (SMT) systems. RSCM can be applied to non-SMT systems but does not always work well on them. This paper proposes an alternative RSCM that adopts a mixture of the N-best lists from multiple MT systems instead of a single-system’s N-best list in the existing RSCM. In most cases, the proposed RSCM proved to work better than the existing RSCM on two non-SMT systems and to work as well as the existing RSCM on an SMT system.