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The thermal management function of high-quality graphene, which is expected to maximize in-plane thermal conductivity at cryogenic temperature, was demonstrated by cryogenic transmission electron microscopy (cryo-TEM) equipped with electron energy loss spectroscopy (EELS). Vitreous ice, observed under the cryo-TEM, suffers from electron beam irradiation, and gradually becomes thinner by sublimation. The ice thickness decreases exponentially with respect to the irradiation time of electron beam with and without graphene, according to the time series of thickness measurement by EELS. Direct contact between graphene and ice effectively dissipates the heat of the ice through graphene, which significantly suppresses the sublimation behavior. The heat dissipation by graphene is effective for thinner ice rather than thicker one. The lifespan of ice on graphene against electron beam irradiation extends to about 40%, showing substantial improvement compared to that without graphene. The graphene provides a new stream for effective thermal management in cryo-TEM analysis.

A novel grid for cryogenic transmission electron microscopy (cryo-TEM) was developed using bilayer graphene to facilitate the formation of a thin ice layer over grid holes. To prepare samples, the bilayer graphene adhered on a holey carbon grid was treated by UV/ozone from the top, making the upper graphene layer hydrophilic, while maintaining the high conductivity via the intact lower layer. Virus solution was loaded on the hydrophilized-graphene surface of the grid, and a thin layer was successfully formed and frozen using an automated blotting system. Inspection in a monochromated cryo-TEM at low-acceleration voltage of 60 kV, provided image of viruses embedded in a very thin vitreous ice layer on bilayer graphene surface, at a high signal-to-noise ratio without charging drifts. The vitreous ice layer formed on the hydrophilized-bilayer graphene surface was homogeneously thin and reached as thin as 25 nm, as confirmed using scanning TEM with electron energy loss spectroscopy. Overall, the high hydrophilicity and homogeneous surface free energy of the UV/ozone-treated bilayer graphene is demonstrated to be highly suitable for thin ice layer preparation, and imaging using cryo-TEM, and especially for modern high-performance low-acceleration voltage TEM, which has higher contrast, but demand thinner ice layers on the grid.

Flavobacterium johnsoniae forms a thin spreading colony on nutrient-poor agar using gliding motility. As reported in the first paper, WT cells in the colony were sparsely embedded in self-produced extracellular polymeric matrix (EPM), while sprB cells were densely packed in immature biofilm with less matrix. The colony surface is critical for antibiotic resistance and cell survival. We have now developed the Grid Stamp-Peel method whereby the colony surface is attached to a TEM grid for negative-staining microscopy. The images showed that the top of the spreading convex WT colonies was covered by EPM with few interspersed cells. Cells exposed near the colony edge made head-to-tail and/or side-to-side contact and sometimes connected via thin filaments. Nonspreading sprB and gldG and gldK colonies had a more uniform upper surface covered by different EPMs including vesicles and filaments. The EPM of sprB, gldG, and WT colonies contained filaments ~2 nm and ~5 nm in diameter; gldK colonies did not include the latter. Every cell near the edge of WT colonies had one or two dark spots, while cells inside WT colonies and cells in SprB-, GldG-, or GldK-deficient colonies did not. Together, our results suggest that the colony surface structure depends on the capability to expand biofilm., International Journal of Molecular Sciences, 22(13), art. no. 6911; 2021

We encountered an 83-year-old man with 3-repeat dominant grain-like tau deposition. Tau-positive lesions exhibited apparent similarity to argyrophilic grains in terms of their distribution in the ambient gyrus, amygdala, and dorsomedial temporal tip and the characteristic comma-like morphology. The abundant oligodendroglial tau immunoreactivities were 3-repeat dominant. Tuft-shaped astrocytes showed partial 3-repeat tau immnoreactivities. These grain-like structures, as well as tuft-shaped astrocytes and oligodendroglia, exhibited predominant 3-repeat tau immunoreactivity, suggesting that grain-like structures and their characteristic distribution are mutually linked and not unique to 4-repeat tau deposition. pTDP immunoreactivity, extensive macrophage infiltration, and spongiosis were associated with these 3-repeat tau deposits.

An 85-year-old man developed l-dopa responsive parkinsonism indistinguishable from Parkinson's disease and subsequent dementia, followed by supranuclear ophthalmoplegia and neck dorsiflexion at the terminal stage. Midbrain tegmentum and medial temporal lobe were atrophic on magnetic resonance imaging, while decreased blood flow was predominant in frontotemporal lobes, detected by 3D-SSP of 123I- IMP SPECT. Alzheimer-type pathology without Lewy body pathology was confirmed at autopsy. Substantia nigra showed mild degeneration and several neurofibrillary tangles without Lewy body pathology or progressive supranuclear palsy cytopathology. L-dopa responsive parkinsonism could be an initial manifestation of Alzheimer's disease, which should be included in the differential diagnosis.

A 75-year-old man developed l-dopa non-responsive parkinsonism, supranuclear ophthalmoplegia, neck dorsiflexion, and dementia. Atrophy of the midbrain tegmentum on MRI and normal myocardial uptake of MIBG led to the clinical diagnosis of progressive supranuclear palsy (PSP). Autopsy revealed depigmentation of the substantia nigra and locus ceruleus. Alzheimer's disease pathology was advanced with PSP-like neurofibrillary tangles distribution, and Lewy bodies were abundant in limbic lobe, while scarce in lower brainstem nuclei. Tuft-shaped astrocytes were not apparent. Although decreased myocardial uptake of MIBG is a rule in patients harboring Lewy bodies, its normal uptake may be related to their absence in lower brainstem nuclei.

We encountered two patients with lesions predominantly localized to the left precentral cortex who presented with speech disorders. Patient 1 had a lesion localized to the anterior part of the left precentral cortex along the precentral sulcus, in the middle part of the convexity. Patient 1 predominantly exhibited disturbance of prosody. Patient 2 had a lesion localized to the left precentral cortex, located slightly more posterior and more inferior in the convexity. Patient 2 predominantly exhibited disturbance of articulation, with distortion of sounds without apparent inconsistency. Even lesions localized to the left precentral cortex present with various types of speech disturbance.

左辺縁葉後端部の小出血で選択的健忘症状を呈した53歳の男性例を報告した.全身痙攣後に一過性意識障害を呈し, 意識障害の改善と共に健忘が明らかになった.健忘は, 言語性優位の著明な前向性健忘と軽度の逆向性健忘で, 障害はエピソード記憶に選択的で, 意味記憶, 手続き記憶は保たれていた.急性期のX線CTでは左辺縁葉後端部に高吸収域を認め, 亜急性期のMRI (T2強調) では同部の皮質と皮質下白質に限局した低信号域を認めた.文献報告例との対比から左辺縁葉後端部病変による健忘は前向性健忘が主体であり, 言語性優位である可能性が示唆された.

Recently, discussions about the clinical features of dentatorubropallidoluysian atrophy (DRPLA), especially the existence of an ataxo-choreoathetoid type, have increased. Traditionally, DRPLA patients have been thought to present with involuntary movements and dementia. Here, we report a patient that presented with ataxia, spasticity of the right lower extremity and mild sensory disturbances. He did not show either apparent involuntary movement or dementia. Mini-mental state examination demonstrated a score of 29/30. The cerebellar output system involving the dentate nuclei and superior cerebellar peduncles seemed to be atrophic yet the cerebellar input system involving the middle cerebellar peduncles was preserved on MRI. In addition, there was an expansion of the atrophin1 (ATN1) CAG repeat of chromosome 12p: 9/61. This seems to be the first case report of a genetically confirmed DRPLA patient presenting with clinical manifestations of Machado-Joseph disease (MJD/SCA3).

Distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM) are genetically identical autosomal recessive muscle disorders caused by mutations in the GNE gene. This gene encodes a bifunctional protein with UDP-GlcNAc 2-epimerase and ManNAc kinase activities that catalyze the rate limiting step and the succeeding step, respectively, in the sialic acid biosynthetic pathway. V572L mutation is the most prevalent among Japanese DMRV patients and accounts for about 60% of mutant alleles. Clinical spectrum of DMRV/HIBM seems to be wider than previously thought in terms of both the severity of the disease and the range of affected organs. There are rare asymptomatic homozygotes with missense GNE mutations, indicating the presence of mitigating factors. Surprisingly, more than 10% of the patients had a variety of cardiac abnormalities, suggesting that skeletal muscle may not be the only organ involved. Studies on recombinant GNE demonstrate a loss-of-function nature of the missense mutations identified. Patients' cells show decreased sialylation status which can be recovered by adding GNE metabolites, such as ManNAc and NeuAc. This indicates the possibility of developing a therapy for DMRV/HIBM by giving these metabolites to patients although we have to await the model mice that are currently being produced at several laboratories.

A 68-year-old man presented with right eye pain and vertigo. Thereafter, he gradually leaned rightward, then laid down. He felt nausea and vomited. His right upper eyelid drooped and he felt dysethesia of the right hand. On neurological examination, ptosis of his right eye with slightly miotic right pupil, paresis of the right soft palate and hoarseness were noted. Arm deviation test demonstrated rightward deviation. He presented sensory ataxia of the right upper and lower extremities: finger nose test showed mild dysmetria of the right upper extremity, heel knee test demonstrated dysmetria of right lower extremity and these findings worsened when he closed his eyes. He showed mild bending of his bilateral ring and little fingers when he did rapid alternative movement. He leaned rightward when he sat and closed his eyes. Position sense of his right upper and lower extremities was decreased and sometimes he could not answer correctly when asked on which direction his finger pointed. Pinprick sensation was mildly decreased on the left side not including the face. Touch and vibration sense were normal. SEP findings on upper and lower extremity stimulation were normal. MRI of the brain showed T2 high intensity and partially T1 low intensity lesion at the right medulla (Figure). MR angiography showed no apparent lesion of major arteries such as dissection of the vertebral arteries. He complained and presented with hiccup initially. On MRI, the lesion was thought to involve the spinothalamic tract, medial lemniscus and inferior olivary nucleus. Ambiguus nucleus was in the lesion and solitary nucleus near the lesion. There is no report that seems to describe clinical features of a lesion like that in this case. Intermediate medullary infarction may present dissociated sensory disturbance like Brown-Sequard syndrome and position sensory disturbance without disturbance of vibration sense.

Background Recently, acute human T-lymphotropic virus type 1–associated myelopathy (HAM) was reported clinically without pathologic information. We report an autopsy case of acute HAM. Objective To report the case of a 52-year-old man with acute-onset gait disturbance followed by rapidly progressive paraplegia, who died 9 months later. Results The postmortem study showed swelling of the thoracic spinal cord. Histologically, there was inflammation and vacuolation in the white matter. Conclusion We propose that these pathologic findings, mimicking tropical spastic paraparesis, may represent the characteristic pathologic features of acute HAM.

To the Editor: We read with interest the recent publication, “Selective Deposition of 4-Repeat Tau in Cerebral Infarcts,” by Ichihara et al (1). The authors reported that Gallyas-positive structures that usually indicate neurodegenerative processes may also appear around ischemic foci. Since Gallyas-positive structures can appear in these apparently distinct processes, it is necessary to distinguish the nature of the process with which they are associated (2). We recently studied …