High-resolution imaging of myosin motor in action by a high-speed atomic force microscope

金沢大学理学部The atomic force microscope (AFM) is a powerful tool for imaging biological molecules on a substrate, in solution. However, there is no effective time axis with AFM; commercially available AFMs require minutes to capture an image, but many interesting biological processes occur at much higher rate. Hence, what we can observe using the AFM is limited to stationary molecules, or those moving very slowly. We sought to increase markedly the scan speed of the AFM, so that in the future it can be used to study the dynamic behaviour of biomolecules. For this purpose, we have developed various devices optimised for high-speed scanning. Combining these devices has produced an AFM that can capture a 100 x 100 pixel image within 80 ms, thus generating a movie consisting of many successive images of a sample in aqueous solution. This is demonstrated by imaging myosin V molecules moving on mica, in solution

Characteristics of urine spraying and scraping the ground with hind paws as scent-marking of captive cheetahs (Acinonyx jubatus)

Olfactory communication is common in felids. We observed two scent-markings, urine spraying and scraping the ground with hind paws during excretion, of 25 captive cheetahs. We analyzed the association of sniffing with the timing of urine spraying and scraping, and differences in these behaviors based on sex, age, and captive environment to understand the olfactory communication among cheetahs. Both scent-markings were strongly associated with sniffing, especially scraping, and the presence or absence of scent was thought to be a trigger. Both behaviors were observed only in adults; scraping was observed only in males. To our knowledge, this study was first to confirm the discharge of secretions from the anal glands during scraping. The frequencies of both behaviors were significantly higher in males kept in shared enclosures containing other individuals than in males kept in monopolized enclosures, while there was no difference in the frequencies among females. Female cheetahs are solitary and have non-exclusive home range, whereas male cheetahs are either solitary or live in coalition groups and there are territorial and non-territorial males. Our results could be attributed to the differences in sociality between the sexes and effect of the living environment

A Case of Isolated Septal Myocardial Infarction: Myocardial Perfusion-Metabolism Mismatch as a Tool for Diagnosis

Isolated septal myocardial infarction is an uncommon condition with diagnostic difficulty due to small infarction size and anatomical variations. We report a case of isolated septal myocardial infarction, in which the diagnosis was confirmed not by electrocardiographic, echocardiographic, or angiographic findings, but by nuclear imaging. A 46-year-old man with chest discomfort exhibited ST-segment elevations in leads V1 and V2, and borderline abnormalities of the septal wall motion on echocardiography. Emergency coronary angiography demonstrated delayed flow in the second septal branch of the left anterior descending coronary artery. Intravascular ultrasound showed plaque in the proximal portion of the septal branch without evidence of plaque rupture. No balloon angioplasty or stent implantation was required because the flow delay in the septal branch disappeared after the intravascular ultrasound procedure. Myocardial perfusion-metabolism mismatch, as assessed by resting thallium-201 and iodine-123-beta-methyl-p-iodophenyl-pentadecanoic acid, was seen in the mid-septal region

Retinol Supplements Antiviral Action of Interferon in Patients with Chronic Hepatitis C: A Prospective Pilot Study

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon α-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks. The retinol group, in addition to above treatment, received retinol 30,000 units per day orally for 3 weeks from one week before the start of interferon α-2b plus ribavirin combination therapy. The hepatitis C virus (HCV) RNA negativity rate at 1 week after the end of interferon α-2b and ribavirin combination therapy was 46.7% (28/60) for the retinol group and 31.7% (19/60) for the control group, which was significantly higher for the retinol group. The level of serum HCV RNA in the retinol group was significantly lower at 1 week after beginning treatment as compared to the control group (p<0.01). Furthermore, serum 2,5'AS protein at 1 week after beginning treatment was significantly higher in the retinol group (p = 0.0002). The results suggest that retinol supplement increases the antiviral effect of interferon α-2b plus ribavirin only during the administration of IFN α-2b, ribavirin and retinol in patients with chronic hepatitis C

Different Patterns of Vascular Response Between Patients With or Without Diabetes Mellitus After Drug-Eluting Stent Implantation Optical Coherence Tomographic Analysis

ObjectivesWe performed this study to investigate with optical coherence tomography (OCT) the vascular response after sirolimus-eluting stent (SES) implantation between patients with and those without diabetes mellitus (DM).BackgroundThe difference in vascular response after SES implantation between patients with and those without DM has not been fully evaluated with OCT.MethodsOptical coherence tomography was performed to examine 74 nonrestenotic SES implanted in 63 patients (32 with DM and 31 without DM) at 9 months after SES implantation. For struts showing neointimal coverage, the neointimal thickness on the luminal side of each strut section was measured, and neointimal characteristics were classified into high, low, and layered signal pattern.ResultsBaseline patient characteristics and lesion and procedural characteristics data were similar between the 2 groups. In total, 11,422 struts were analyzed. High signal neointima was observed in 90.2 ± 13.9%, low signal neointima in 7.3 ± 10.0%, and layered neointima in 2.7 ± 5.8%/stents. There was higher incidence of low signal neointima (10.5 ± 10.3% vs. 4.5 ± 5.6%, p = 0.003), neointimal thickness was larger (median: 106.8 μm, interquartile range: 79.3 to 130.4 μm vs. median: 83.5 μm, interquartile range: 62.3 to 89.3 μm; p < 0.0001), and neointimal coverage of stent struts was higher (92.1 ± 6.2% vs. 87.2 ± 11.9%; p = 0.03) in DM patients.ConclusionsHigh signal neointimal pattern was predominantly observed, and low or layered signal pattern was observed in some cases. In DM patients, low signal neointima was observed with high frequency. Neointimal coverage and neointimal thickness was also higher in DM patients as compared with non-DM patients

Aging Is a Risk Factor for Utricular Dysfunction in Idiopathic Benign Paroxysmal Positional Vertigo

Benign paroxysmal positional vertigo (BPPV) is the most common cause of balance disorders in the elderly. Dislodgement of the otoconia in BPPV might have an association with damage to the otolith organs. The aim of this study was to investigate whether aging is a risk factor for otolith organ dysfunction in idiopathic BPPV. We retrospectively reviewed the medical records of 112 consecutive idiopathic BPPV patients who underwent cervical VEMP testing to air-conducted sound (ACS cVEMP), ocular VEMP testing to bone-conducted vibration (BCV oVEMP), and caloric testing. We performed binomial logistic regression analyses to see whether age, the side affected by BPPV or the canal affected by BPPV have an association with the presence of peripheral vestibular dysfunction in idiopathic BPPV patients. The elderly group (aged ≥65 years) had a significantly positive association with abnormalities in BCV oVEMPs (p = 0.0109), while the side affected by BPPV (p = 0.598) and the canal affected by BPPV (p = 0.576) did not. The odds ratio of the abnormal BCV oVEMPs for the elderly group compared with the non-elderly group (aged &lt; 65 years) was 2.676 (95% confidence interval, 1.254–5.079). The elderly group had no significant association with the abnormalities in ACS cVEMPs (p = 0.0955) or caloric testing (p = 0.488). Dysfunction of the utricle, where the dislodgement of the otoconia mainly occurs, is affected by aging in idiopathic BPPV

A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models

Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia