Coupling between pore formation and phase separation in charged lipid membranes

We investigated the effect of charge on the membrane morphology of giant unilamellar vesicles (GUVs) composed of various mixtures containing charged lipids. We observed the membrane morphologies by fluorescent and confocal laser microscopy in lipid mixtures consisting of a neutral unsaturated lipid [dioleoylphosphatidylcholine (DOPC)], a neutral saturated lipid [dipalmitoylphosphatidylcholine (DPPC)], a charged unsaturated lipid [dioleoylphosphatidylglycerol (DOPG$^{\scriptsize{(-)}}$)], a charged saturated lipid [dipalmitoylphosphatidylglycerol (DPPG$^{\scriptsize{(-)}}$)], and cholesterol (Chol). In binary mixtures of neutral DOPC/DPPC and charged DOPC/DPPG$^{\scriptsize{(-)}}$, spherical vesicles were formed. On the other hand, pore formation was often observed with GUVs consisting of DOPG$^{\scriptsize{(-)}}$ and DPPC. In a DPPC/DPPG$^{\scriptsize{(-)}}$/Chol ternary mixture, pore-formed vesicles were also frequently observed. The percentage of pore-formed vesicles increased with the DPPG$^{\scriptsize{(-)}}$ concentration. Moreover, when the head group charges of charged lipids were screened by the addition of salt, pore-formed vesicles were suppressed in both the binary and ternary charged lipid mixtures. We discuss the mechanisms of pore formation in charged lipid mixtures and the relationship between phase separation and the membrane morphology. Finally, we reproduce the results seen in experimental systems by using coarse-grained molecular dynamics simulations.Comment: 34 pages, 10 figure

Diagnostic sensitivity of motor nerve conduction studies in ulnar neuropathy at the elbow.

Seventy-six patients with ulnar neuropathy at the elbow were divided into 3 classes (Grades I, II, and III) according to their clinical features and the maximal motor nerve conduction velocity (MCV), and the amplitude ratios at the across-elbow segment were retrospectively analyzed. To determine the criteria for abnormality, a control study was conducted on 150 healthy volunteers ranging in age from 20 to 89 years (6 age groups). The normal value for MCV could be set for two age groups: those under 60 and those over 60 years old. The 95% confidence limit was 54m/s for the former and 50m/s for the latter. There was no statistically significant difference in the amplitude ratio among the age groups. The confidence limit was set uniformly at 0.82 (above elbow/below elbow). An abnormality in either MCV or the amplitude ratio was found in 66.7% of Grade I (recent and mild symptoms), 89.7% of Grade II (persistent symptoms), and 100% of Grade III cases (marked intrinsic muscle atrophy). Evaluation using the combination of MCV and the amplitude ratio, considering the age-related normal value, appeared to be useful in establishing a differential diagnosis of ulnar neuropathy at the elbow.</p

How Is the Fee Decided?

展示を考える1 What Is a Museum Exhibition

05 大学院における博物館学専攻プログラム

大学院における高度専門職学芸員養成プログラムの提

Serotonergic Control of Brain-Wide Dynamics

Serotonin, one of the neuromodulators, is associated with multiple functions, such as the wake-sleep cycle, decision making, and mood. Serotonin is also the primary tar-get of medication for major depression (MD), notably by selective serotonin re-uptake inhibitors (SSRIs). However, it is widely known that serotonergic antidepressants re-quire long-term administration, and acute medication sometimes worsens symptoms.Serotonergic regulation of brain-wide dynamics remains crucial for understanding its roles in behavioral and cognitive functions as well as the mechanism of antidepressant medication. First, I studied the influences of a serotonergic antidepressant on brain dynamics with functional magnetic resonance imaging in rodents. I found that the functional connectivity between the bed nucleus of steria terminalis (BST) and the ventral retrosplenial cortex (vRSC) distinctively responded to acute serotonergic antidepressant treatment, escitalopram. Additionally, long-term serotonergic antidepressant treatment promoted spontaneous locomotion and influenced anxiety like behaviors only in context-dependent and individually variable ways. The results imply that long-term serotonergic antidepressant treatment enhances intrinsic motivation,but not anxiety. Additionally, I analyzed large-scale brain dynamics with functional connectivity analysis and energy landscape analysis (ELA). My ELA analysis revealed that chronic administration of serotonergic antidepressants maintained dynamic brain states linking major attractor states, while conventional functional connectivity (FC)analysis did not show any difference caused by serotonergic antidepressants. The intermediate brain states, which are supported by modular integration, are associated with active exploration. My findings suggest that serotonergic antidepressants induce resilience by stabilizing brain state dynamics as a result of shaping functional network architecture. In the second study, I conducted a pilot experiment to assess serotonergic modulation of brain dynamics by optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN). In the first animal test, I found brain responses in the frontal cortical regions (the anterior cingulate cortex, the medial prefrontal cortex, and the insular cortex), the striatum, and the ventral tegmental area (VTA). In a reward delay task, optogenetic activation of DRN serotonin neurons enhanced waiting for delayed rewards, which confirmed the effectivenss of optogenetic stimulation. The result suggested the feasibility of studying serotonergic modulation with opto-fMRI. My thesis delineates how the serotonergic system regulates brain-wide dynamics at short- and long-term scales.Okinawa Institute of Science and Technology Graduate Universit

Intra-articular osteoid osteoma of the calcaneus: a case report and review

AbstractOsteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis