Showing papers by "Gifu University of Medical Science published in 2019"

Myogenin promoter‐associated lncRNA Myoparr is essential for myogenic differentiation

Abstract: Promoter-associated long non-coding RNAs (lncRNAs) regulate the expression of adjacent genes; however, precise roles of these lncRNAs in skeletal muscle remain largely unknown. Here, we characterize a promoter-associated lncRNA, Myoparr, in myogenic differentiation and muscle disorders. Myoparr is expressed from the promoter region of the mouse and human myogenin gene, one of the key myogenic transcription factors. We show that Myoparr is essential both for the specification of myoblasts by activating neighboring myogenin expression and for myoblast cell cycle withdrawal by activating myogenic microRNA expression. Mechanistically, Myoparr interacts with Ddx17, a transcriptional coactivator of MyoD, and regulates the association between Ddx17 and the histone acetyltransferase PCAF Myoparr also promotes skeletal muscle atrophy caused by denervation, and knockdown of Myoparr rescues muscle wasting in mice. Our findings demonstrate that Myoparr is a novel key regulator of muscle development and suggest that Myoparr is a potential therapeutic target for neurogenic atrophy in humans.

Renin-angiotensin System Blockade Therapy for Early Renal Involvement in MYH9-related Disease with an E1841K Mutation.

Abstract: MYH9-related disease is a rare genetic disorder characterized by macrothrombocytopenia, with frequent proteinuric nephropathy, hearing loss, and cataract. Although proteinuric nephropathy usually progresses to renal failure, there is no established treatment for the nephropathy. We herein describe the case of a 19-year-old man carrying an E1841K MYH9 mutation, who developed persistent proteinuria. The patient was diagnosed with early-stage MYH9-related nephropathy based on the histological examination of a kidney biopsy specimen. The patient was treated with enalapril, which significantly reduced the proteinuria with no decline in his renal function. The early administration of renin-angiotensin system blockade therapy may have beneficial effects on MYH9-related nephropathy in patients with E1841K mutations. We also briefly summarize previously published cases of MYH9-related nephropathy treated with renin-angiotensin system (RAS) blockade therapy.

Contrasting open-loop dynamic characteristics of sympathetic and vagal systems during baroreflex-mediated heart rate control in rats.

Abstract: Although heart rate (HR) is governed by the sympathetic and parasympathetic nervous systems, a head-to-head comparison of the open-loop dynamic characteristics of the total arc from a baroreceptor ...

A novel mammographic fusion imaging technique: the first results of tumor tissues detection from resected breast tissues using energy-resolved photon counting detector

Abstract: We developed a prototype photon-counting mammography unit with a cadmium zinc telluride detector, which provides a new type of image with physical analysis parameters. Using the X-ray attenuation information obtained from this device, we examined the ability of this technique in discriminating substances and estimating their compositions. To estimate the substance compositions, we used resected breast tissues immediately after a surgical operation for invasive carcinoma of no special type, and used phantoms to reproduce mammary glands and adipose tissue. In our system, the spectrum penetrating the substance was measured with three energy bins in each pixel. The products of linear-attenuation coefficient and thicknesses for each bin were calculated. Using these three values, the scatterplots displaying all the values calculated from each pixel inside the region of interest (ROI) on the image were created. The scatterplot displaying only gravity values calculated for each ROI on the image was created for evaluating the separation of plot points to discriminate between different substance compositions. The gravity points placed on the malignant tumor tissue were plotted separately from those on the normal tissue. Furthermore, a fusion image was created by overlapping an X-ray image and values of this scatterplot points represented on a 10-step color scale. The fusion image was highlighting the differences in substance compositions using color tone, such as malignant tumor or mammary gland tissue, by adjusting the color scale level.

[Selection of Radiomic Features for the Classification of Triple-negative Breast Cancer Based on Radiogenomics].

Abstract: Subtype classification of breast cancer by analyzing the gene expression profile of cancer cells is becoming a standard procedure. Breast cancer subtype classification is more useful than the conventional method because the characteristics of subtype classification is directly connected with the treatment method. However, genetic testing is invasive, and a part of cancer cells may not represent the overall nature of the cancer. In the computer-aided diagnosis (CAD) scheme for differentiation of triple-negative breast cancer (TNBC) by estimating the genetic properties of cancer based on Radiogenomics, principal component analysis (PCA) and least absolute shrinkage and selection operator (Lasso) were used for reducing the dimension of radiomic features, and we compared usefulness of both. We collected 81 magnetic resonance (MR) images, which included 30 TNBC and 51 others, from the public database. From the MR slice images, we selected the slice containing the largest area of the cancer and manually marked the cancer region. We subsequently calculated 294 radiomic features in the cancer region, and reduced the dimension of radiomic features. Finally, linear discriminant analysis, with the dimensionally compressed 10 image features, was used for distinguishing between TNBC and others. Area under the curve (AUC) was 0.60 when we used PCA, whereas AUC was 0.70 when we used Lasso (p=0.0058). Therefore, Lasso is useful for the determination of radiomic features in Radiogenomics.

Novel ACTN1 variants in cases of thrombocytopenia.

Abstract: The ACTN1 gene has been implicated in inherited macrothrombocytopenia. To decipher the spectrum of variants and phenotype of ACTN1-related thrombocytopenia, we sequenced the ACTN1 gene in 272 cases of unexplained chronic or familial thrombocytopenia. We identified 15 rare, monoallelic, nonsynonymous and likely pathogenic ACTN1 variants in 20 index cases from 20 unrelated families. Thirty-one family members exhibited thrombocytopenia. Targeted sequencing was carried out on 12 affected relatives, which confirmed presence of the variant. Twenty-eight of 32 cases with monoallelic ACTN1 variants had mild to no bleeding complications. Eleven cases harbored 11 different unreported ACTN1 variants that were monoallelic and likely pathogenic. Nine variants were located in the α-actinin-1 (ACTN1) rod domain and were predicted to hinder dimer formation. These variants displayed a smaller increase in platelet size compared with variants located outside the rod domain. In vitro expression of the new ACTN1 variants induced actin network disorganization and led to increased thickness of actin fibers. These findings expand the repertoire of ACTN1 variants associated with thrombocytopenia and highlight the high frequency of ACTN1-related thrombocytopenia cases. The rod domain, like other ACTN1 functional domains, may be mutated resulting in actin disorganization in vitro and thrombocytopenia with normal platelet size in most cases.

Anagrelide Modulates Proplatelet Formation Resulting in Decreased Number and Increased Size of Platelets.

Abstract: We retrospectively evaluated 48 essential thrombocythemia (ET) patients who were treated in our institute (male/female, 14/34, median age, 61.5 years). In 14 patients treated with anagrelide (ANA), the degree of platelet count reduction (median, -56.6%) was strongly correlated with increase of mean platelet volume (MPV) (median, +11.7%) (R = 0.777). This correlation was not observed in ET patients treated with hydroxycarbamide alone (R = 0.245). The change in size of platelets strongly suggested that ANA affected the final process of platelet production. Thus, we hypothesized that ANA modifies the process by which platelets are released from proplatelets. To verify the association in an in vitro setting, we compared MEG-01 cells treated with PMA ± ANA. The number of platelet-like particles (PLPs) was decreased (P < 0.05) and the size of PLPs estimated by using flow cytometry was significantly increased when MEG-01 cells were treated with PMA + ANA (P < 0.05 vs PMA alone), recapitulating the clinical findings. The cytoplasmic protrusions extending from MEG-01 cells were shorter and thicker and the number of proplatelets was decreased when MEG-01 cells were treated with PMA + ANA (P < 0.01 vs PMA alone). Western blotting analysis showed that ANA treatment resulted in increased phosphorylation of MLC2 and reduced phosphorylation of focal adhesion kinase (FAK). The morphological change of proplatelets were reversed by blebbistatin, a specific inhibitor of myosin II. These findings indicated that ANA modulates the FAK-RhoA-ROCK-MLC2-myosine IIA pathway and suppresses proplatelet maturation, leading to a decrease in platelet count and increase in MPV.

Normal generation and covers of small degree

Abstract: Let L be a special very ample line bundle of degree deg(L) on a curve X with sufficiently high genus g. We show that L is normally generated if deg(L)≥2g−2s+1−2(s+1)h1(L)(s≥2) and X is not ...

Changes in Eye Movements and Body Sway While Viewing Stereoscopic Movies Under Controlled Consciousness

Abstract: In our previous study, we found that it is possible to have an effect of change in the condition of consciousness (allocation of consciousness) on visually evoked postural responses (VEPRs) and subjective symptoms of visually induced motion sickness (VIMS) Thus, in this study, we verified the effect of controlling consciousness on body sway and eye movements while participants viewed stereoscopic movies Participants watched a three-dimensional movie consisting of several colored balls that moved sideways sinusoidally at 025 Hz for 180 s after pre-instruction Pre-instructions included “uncontrolled consciousness,” “keep a static, upright posture,” and “sway body in the same/opposite direction” This study recorded both center of pressure, as body sway, and electrooculography (EOG) data, as eye movements Recorded EOG data were converted to eye movement velocity The results clearly showed that (1) the influence of the pre-instruction appeared to be much stronger than that of the VEPRs, (2) the pre-instruction changed the frequency of the saccade, or interquartile range of eye movement, velocity histogram according to each task as measured by changes in retinal slip velocity, and (3) the condition of consciousness that controlled body motion changed the participants’ postural instability and eye movement results Thus, after considering many theories for the origin of VIMS, we concluded that the condition of consciousness controlled VIMS

Tablet Computers and Their Effect on Sleep Onset

Abstract: This chapter discusses about tablet computers, which are being increasingly used by the general public and in households, and the effect of their use on the onset of sleep. Recently, it has been suggested that devices containing light-emitting diode (LED)-backlit liquid crystal displays (LCDs), like tablet computers, should not be used in the evening because continuous exposure to strong light causes melatonin suppression and thus contributes to circadian rhythm disturbances (increase in the degree of awareness). Previous related studies have reported inconsistent findings on the relationship between melatonin suppression and increase in the degree of awareness. We assumed the existence of a physiological factor capable of interrupting the onset of sleep regardless of suppressing melatonin. In particular, we focused on cerebral activity. Our hypothesis was that using devices with LED-backlit LCDs changes cerebral activity required for the onset of sleep. This chapter describes our comparative study on cerebral activity using near-infrared spectroscopy (NIRS) for functional brain imaging in order to demonstrate the above hypothesis; participants read from either a printed book or a tablet computer. From this study, we concluded that reading a book on a tablet computer before sleep onset leads to the potential inhibition of comfortable sleep through mechanisms other than the suppression of melatonin secretion.