Search

The case is an 80-year-old woman with Sjögren's syndrome. During the follow-up of multiple pulmonary nodules, an enlarged nodule was observed in the peripheral of the right S3 interlobar region. Fluorodeoxyglucose- positron emission tomography (FDG-PET) showed FDG accumulation only in the S3 nodule, which led to suspicion of primary lung cancer. Because of its difficult location to reach by bronchoscopy, a right lung S3 segmentectomy was performed. Intraoperative findings revealed a hard yellowish- white nodule just below the pleura. Pathological examination showed that the nodule consisted of an acidophilic structureless material, which was positive for Congo red staining and disappeared after permanganate treatment. Based on the above findings, we diagnosed amyloid A( AA)-type amyloidosis. In this case, the nodule was located just below the pleura and we could observe it by thoracoscopy. There have been few reports of thoracoscopic observation of pulmonary amyloidosis, and we report with intraoperative findings.

Quantum communication, and more specifically Quantum Key Distribution (QKD), enables the transmission of information in a theoretically secure way, guaranteed by the laws of quantum physics. Although fiber-based QKD has been readily available since several years ago, a global quantum communication network will require the development of space links, which remains to be demonstrated. NICT launched a LEO satellite in 2014 carrying a lasercom terminal (SOTA), designed for in-orbit technological demonstrations. In this paper, we present the results of the campaign to measure the polarization characteristics of the SOTA laser sources after propagating from LEO to ground. The most-widely used property for encoding information in free-space QKD is the polarization, and especially the linear polarization. Therefore, studying its behavior in a realistic link is a fundamental step for proving the feasibility of space quantum communications. The results of the polarization preservation of two highly-polarized lasers are presented here, including the first-time measurement of a linearly-polarized source at λ = 976 nm and a circularly-polarized source at λ = 1549 nm from space using a realistic QKD-like receiver, installed in the Optical Ground Station at the NICT Headquarters, in Tokyo, Japan.

Autophagy is a conserved eukaryotic process of protein and organelle self-degradation within the vacuole/lysosome. Autophagy is characterized by the formation of an autophagosome, for which Vps34-dervied phosphatidylinositol 3-phosphate (PI3P) is essential. In yeast, Vps34 forms two distinct protein complexes: complex I, which functions in autophagy, and complex II, which is involved in protein sorting to the vacuole. Here we identify and characterize Atg38 as a stably associated subunit of complex I. In atg38Δ cells, autophagic activity was significantly reduced and PI3-kinase complex I dissociated into the Vps15-Vps34 and Atg14-Vps30 subcomplexes. We find that Atg38 physically interacted with Atg14 and Vps34 via its N terminus. Further biochemical analyses revealed that Atg38 homodimerizes through its C terminus and that this homodimer formation is indispensable for the integrity of complex I. These data suggest that the homodimer of Atg38 functions as a physical linkage between the Vps15-Vps34 and Atg14-Vps30 subcomplexes to facilitate complex I formation.

Autophagy is a bulk degradation system mediated by biogenesis of autophagosomes under starvation conditions. In Saccharomyces cerevisiae, a membrane sac called the isolation membrane (IM) is generated from the pre-autophagosomal structure (PAS); ultimately, the IM expands to become a mature autophagosome. Eighteen autophagy-related (Atg) proteins are engaged in autophagosome formation at the PAS. However, the cup-shaped IM was visualized just as a dot by fluorescence microscopy, posing a challenge to further understanding the detailed functions of Atg proteins during IM expansion. In this study, we visualized expanding IMs as cup-shaped structures using fluorescence microscopy by enlarging a selective cargo of autophagosomes, and finely mapped the localizations of Atg proteins. The PAS scaffold proteins (Atg13 and Atg17) and phosphatidylinositol 3-kinase complex I were localized to a position at the junction between the IM and the vacuolar membrane, termed the vacuole-IM contact site (VICS). By contrast, Atg1, Atg8 and the Atg16-Atg12-Atg5 complex were present at both the VICS and the cup-shaped IM. We designate this localization the 'IM' pattern. The Atg2-Atg18 complex and Atg9 localized to the edge of the IM, appearing as two or three dots, in close proximity to the endoplasmic reticulum exit sites. Thus, we designate these dots as the 'IM edge' pattern. These data suggest that Atg proteins play individual roles at spatially distinct locations during IM expansion. These findings will facilitate detailed investigations of the function of each Atg protein during autophagosome formation.

Nonfibrillar assemblies of amyloid β-protein (Aβ) are considered to play primary roles in Alzheimer disease (AD). Elucidating the assembly pathways of these specific aggregates is essential for understanding disease pathogenesis and developing knowledge-based therapies. However, these assemblies cannot be monitored in vivo, and there has been no reliable in vitro monitoring method at low protein concentration. We have developed a highly sensitive in vitro monitoring method using fluorescence correlation spectroscopy (FCS) combined with transmission electron microscopy (TEM) and toxicity assays. Using Aβ labeled at the N terminus or Lys(16), we uncovered two distinct assembly pathways. One leads to highly toxic 10-15-nm spherical Aβ assemblies, termed amylospheroids (ASPDs). The other leads to fibrils. The first step in ASPD formation is trimerization. ASPDs of ∼330 kDa in mass form from these trimers after 5 h of slow rotation. Up to at least 24 h, ASPDs remain the dominant structures in assembly reactions. Neurotoxicity studies reveal that the most toxic ASPDs are ∼128 kDa (∼32-mers). In contrast, fibrillogenesis begins with dimer formation and then proceeds to formation of 15-40-nm spherical intermediates, from which fibrils originate after 15 h. Unlike ASPD formation, the Lys(16)-labeled peptide disturbed fibril formation because the Aβ(16-20) region is critical for this final step. These differences in the assembly pathways clearly indicated that ASPDs are not fibril precursors. The method we have developed should facilitate identifying Aβ assembly steps at which inhibition may be beneficial.

Purpose: The anti-aquaporin-4 (AQP4) antibody was recently reported to be associated with neuromyelitis optica (NMO). Optic nerve involvements in many NMO cases are bilateral and the prognosis is poor. However, it has been suggested that plasma exchange is effective for those patients when steroid pulse therapy is ineffective. Herein, we report successful treatment of a patient with NMO using double-filtration plasmapheresis (DFPP)., Case: A 22-year-old woman consulted a neurologist for neck pain in March 2008. High-intensity lesions were shown in the cervical spinal cord by T2-weighted magnetic resonance imaging. On July 15, the patient was referred to our department for a headache and pain and blurred vision in the left eye. The best-corrected visual acuity was 20/50 and 20/500 in the right and left eyes, respectively, with visual field defects observed in both. After 3 courses of steroid pulse therapy, anti-AQP4 antibodies were positive. In November, the patient again noticed visual acuity loss in the left eye and was treated by additional steroid pulse therapy, which was not effective. Next, she underwent plasma exchange therapy, though it was stopped due to hypotension and dyspnea. The next day, the patient underwent DFPP treatment and visual function gradually recovered., Conclusion: It is important to consider NMO when steroid pulse therapy is not effective. We successfully and safely treated NMO in a young adult patient using DFPP.

Amyloid beta-protein (Abeta) assemblies are thought to play primary roles in Alzheimer disease (AD). They are considered to acquire surface tertiary structures, not present in physiologic monomers, that are responsible for exerting toxicity, probably through abnormal interactions with their target(s). Therefore, Abeta assemblies having distinct surface tertiary structures should cause neurotoxicity through distinct mechanisms. Aiming to clarify the molecular basis of neuronal loss, which is a central phenotype in neurodegenerative diseases such as AD, we report here the selective immunoisolation of neurotoxic 10-15-nm spherical Abeta assemblies termed native amylospheroids (native ASPDs) from AD and dementia with Lewy bodies brains, using ASPD tertiary structure-dependent antibodies. In AD patients, the amount of native ASPDs was correlated with the pathologic severity of disease. Native ASPDs are anti-pan oligomer A11 antibody-negative, high mass (>100 kDa) assemblies that induce degeneration particularly of mature neurons, including those of human origin, in vitro. Importantly, their immunospecificity strongly suggests that native ASPDs have a distinct surface tertiary structure from other reported assemblies such as dimers, Abeta-derived diffusible ligands, and A11-positive assemblies. Only ASPD tertiary structure-dependent antibodies could block ASPD-induced neurodegeneration. ASPDs bind presynaptic target(s) on mature neurons and have a mode of toxicity different from those of other assemblies, which have been reported to exert their toxicity through binding postsynaptic targets and probably perturbing glutamatergic synaptic transmission. Thus, our findings indicate that native ASPDs with a distinct toxic surface induce neuronal loss through a different mechanism from other Abeta assemblies.