PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids.

The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain.

PET/computed tomography shows association between subjective pain in knee joints and fluorine-18-fluorodeoxyglucose uptake.

OBJECTIVE: The aim of this study was to evaluate the capability of fluorine-18-fluorodeoxyglucose (F-FDG)-PET/computed tomography (CT) in screening for musculoskeletal inflammation and injury in the knee region. METHODS: The study included 12 subjects (6 men and 6 women) who complained of knee pain at rest and 94 controls who did not. Maximum standardized uptake value (SUV)max was calculated for the right and left knees and compared via a 4-point numerical rating scale (NRS) for subjective knee pain. Correlations between SUV values were also evaluated. RESULTS: SUVmax was significantly higher in knee joints with resting and/or walking pain than in pain-free knee joints. SUVmax in knee joints with walking pain were significantly correlated with NRS category (ß = 0.129, P < 0.001). CONCLUSION: F-FDG-PET/CT may be useful in screening for musculoskeletal inflammation and injury in the knee region. As knee pain is common, especially among elderly individuals, we should consider conducting further examinations when F-FDG uptake is identified in knee joints.

Uptake of aortic 18F-FDG is correlated with low-density lipoprotein cholesterol and leptin in a general population.

OBJECTIVE: This study investigated the relationship between aortic 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to atherosclerosis in a general population. METHODS: 18F-FDG uptake in the ascending aorta was measured on the positron emission tomography/computed tomography (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio (TBR) was compared with clinical and laboratory atherosclerosis findings. RESULTS: By multivariate regression analysis adjusted for age and sex, TBR-ascending aorta (TBR-A) was significantly correlated with various clinical and laboratory parameters, such as body mass index, log visceral fat area, low-density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log homeostasis model assessment of insulin resistance, log total adiponectin and log-leptin, in all subjects. Furthermore, by multivariate linear regression analysis adjusted for confounding factors, TBR-A was significantly correlated with LDL-C (ß = 0.001, p = 0.03) and log-leptin (ß = 0.336, p<0.01) in all subjects. CONCLUSION: TBR-A was significantly correlated with LDL-C and log-leptin independent from confounding factors. Our results suggest that aortic 18F-FDG uptake is a good marker of atherosclerosis, even in a general population.

PET/CT shows subjective pain in shoulder joints to be associated with uptake of (18)F-FDG.

OBJECTIVES: The aim of the study was to evaluate the capability of fluorine-18-fluorodeoxyglucose (F-FDG)-positron emission tomography (PET)/computed tomography (CT) in the screening of musculoskeletal inflammation and injury of the shoulder region. MATERIALS AND METHODS: The study included 122 participants (69 men and 53 women) who complained of shoulder pain at rest and 122 age-matched and sex-matched controls who did not experience pain at rest. Standardized uptake values (SUVs) were calculated for both the left and right shoulders and compared using a four-point visual analog scale of subjective shoulder pain. Correlations between SUVs and uric acid and C-reactive proteins were also evaluated. RESULTS: SUVs for shoulder joints with rest and/or motion pain were significantly higher than those for pain-free shoulder joints. SUVs associated with mild and severe pain at rest were significantly higher than those associated with absence of pain at rest, and SUVs associated with moderate and severe pain on motion were significantly higher than those associated with absence of motion pain. Furthermore, SUVs were significantly correlated with uric acid in men (ß=0.21, P=0.02) and in all participants (ß=0.22, P<0.001). CONCLUSION: F-FDG-PET/CT may be useful for the screening of musculoskeletal inflammation and injury of the shoulder region. As shoulder pain is common, especially among elderly individuals, we should carefully consider the necessity of further examination when identifying the uptake of F-FDG in shoulder joints.

Observation of cortical activity during speech stimulation in prelingually deafened adults with cochlear implantation by positron emission tomography-computed tomography.

OBJECTIVES: We evaluated the cortical activity of 2 successful prelingually deafened adult cochlear implant (CI) users who have been trained by auditory-verbal/oral communication since childhood. METHODS: Changes in regional cerebral blood flow were measured by positron emission tomography using '8F-fluorodeoxyglucose while the subjects were receiving auditory language stimuli by listening to a story. Ten normal-hearing volunteers were observed as age-matched control subjects. RESULTS: In both cases, the auditory-related regions, when compared to same regions in the control subjects, showed hypermetabolism in the left dorsolateral prefrontal cortex and the left precentral gyrus--similar to that in successful CI users who are prelingually deafened children or postlingually deafened adults. Both subjects had the ability to activate these areas, and this ability might be one of the reasons that accounts for such exceptionally good performance in older prelingually deaf CI users. As for the visual-related regions, hypometabolism was observed in Brodmann areas 18 and 19, and this finding might be related to the intensive auditory-verbal/oral education that the subjects had received since childhood. CONCLUSIONS: Despite the limits imposed by the small sample size and the spatial resolution of positron emission tomography, this study yielded insights into the nature of the brain plasticity in prelingually deafened adults who are successful CI users.

Effect of sequential applications of topical tacrolimus and topical corticosteroids in the treatment of pediatric atopic dermatitis: an open-label pilot study.

BACKGROUND: The efficacy of combination therapy with topical corticosteroids and tacrolimus in the treatment of atopic dermatitis remains to be established. OBJECTIVE: Our aim was to determine whether a regimen of sequential application of topical corticosteroids and topical tacrolimus is effective in the treatment of pediatric atopic dermatitis. A second goal was to assess the impact of this treatment regimen on quality of life (QOL) and the response shift on QOL changes. METHODS: The study regimen consisted of 3 phases. In the induction phase, patients were treated for a 2-week period with application of 0.03% tacrolimus ointment in the morning and application of a strong- or weak-potency corticosteroid ointment in the evening. In the transitional phase, they were treated for an additional 2 weeks with 0.03% tacrolimus ointment twice daily on weekdays and concurrent application of tacrolimus and a topical corticosteroid ointment on weekend days. In the maintenance phase, the corticosteroid ointment was discontinued and 0.03% tacrolimus ointment was applied twice daily for an additional 2 weeks. Daily application of tacrolimus ointment was then discontinued and replaced by an emollient with application of 0.03% tacrolimus ointment only when necessary for an additional 6 weeks. The Eczema Area and Severity Index score, Investigators' Global Assessment, severity of pruritus and sleep disturbance scores, and QOL evaluation were measured. After 12 weeks, the patients completed a retrospective version of the pretreatment QOL evaluation for analysis of response shift bias. RESULTS: Eczema Area and Severity Index scores decreased by the sixth week, and continued improvement was observed during an additional 6-week period. Both the pruritus and sleep disturbance scores decreased throughout the study. Of patients, 90% showed marked clinical improvement at week 6 and 96% at week 12. On the Children's Dermatology Life Quality Index and the Infant's Dermatology QOL Index survey, mean QOL scores improved after completion of therapy at week 12. The mean difference between the pretest and the retrospective pretest scores indicated the presence of a response shift bias. LIMITATIONS: This was an uncontrolled, open-label study. Conclusions are limited by the small sample size. CONCLUSIONS: A fixed sequential regimen of application of tacrolimus ointment with tapering of topical corticosteroids may limit the long-term use and adverse effects of topical corticosteroids, while maintaining clinical control of pediatric atopic dermatitis and improving the QOL. The finding of a response shift bias suggests that parents/guardians underestimate the seriousness of skin disease and its impact on QOL.