Genome-wide identification of tandem repeats associated with splicing variation across 49 tissues in humans.

Tandem repeats (TRs) are one of the largest sources of polymorphism, and their length is associated with gene regulation. Although previous studies reported several tandem repeats regulating gene splicing in cis (spl-TRs), no large-scale study has been conducted. In this study, we established a genome-wide catalog of 9537 spl-TRs with a total of 58,290 significant TR-splicing associations across 49 tissues (false discovery rate 5%) by using Genotype-Tissue expression (GTex) Project data. Regression models explaining splicing variation by using spl-TRs and other flanking variants suggest that at least some of the spl-TRs directly modulate splicing. In our catalog, two spl-TRs are known loci for repeat expansion diseases, spinocerebellar ataxia 6 (SCA6) and 12 (SCA12). Splicing alterations by these spl-TRs were compatible with those observed in SCA6 and SCA12. Thus, our comprehensive spl-TR catalog may help elucidate the pathomechanism of genetic diseases.

Successful Treatment of Full Thickness Frontal Skull Bone Defect With Dermal Fat Grafting and Artificial Bone Grafts.

Rigid reconstruction for frontal bone defects not only improves function, but also approximates more normal appearance. However, in cases involving dural scar contractures, a concave deformation remains when rigid reconstruction is performed without compensating for dead space created by swelling of the brain. This study involved 4 cases in which a 2-stage reconstruction procedure was used to first eliminate dead space by grafting dermal fat, and subsequently carry out rigid reconstruction to achieve a natural forehead configuration. This method is advantageous and considered to be effective in allowing dead space to be easily filled with minimal invasiveness for concave deformations of the dura mater with bone defects. Furthermore, the risk of artificial bone exposure is reduced by adding the dermal component of dermal fat, which is grafted to thinned frontal skin.

Osteoid osteoma of the temporal bone manifesting as first bite syndrome and a meta-analysis combined with osteoblastoma.

The objectives of this study were to describe a case of osteoid osteoma arising from the temporal bone manifesting only as first bite syndrome as the sole clinical symptom, to perform a meta-analysis of previously reported cases, and to differentiate the clinical characteristics of osteoid osteoma from those of osteoblastoma arising from the temporal bone. In addition to our case, articles addressing osteoid osteoma or osteoblastoma arising from the temporal bone were selected using PubMed, Embase, and the Japan Medical Abstracts Society database (1954 through 2014), with no language preference. The database was searched using the keywords ["osteoid osteoma" OR "osteoblastoma" AND "temporal bone"]. After critical review of 88 studies, 10 cases of osteoid osteoma and 29 cases of osteoblastoma were selected; therefore, including the present case, a total of 40 cases were eligible for qualitative analyses. The mean size of osteoid osteoma was 1.2 cm, which was significantly smaller than that of osteoblastoma (5.1 cm). Radiologically, osteoid osteoma was associated with a lower prevalence of extension into more than two anatomically categorized spaces in comparison with osteoblastoma (P < 0.01). Again, a lower prevalence of erosion of the outer and/or inner tables of the skull in the osteoid osteoma cases was noted (P < 0.05). Conversely, there were no significant differences in the prevalence of representative clinical symptoms, including pain and swelling. According to the present systematic review, osteoid osteoma and osteoblastoma are clinically uniform other than their size or extension.

Hydroxoiridium-Catalyzed Hydroalkylation of Terminal Alkenes with Ureas by C(sp3 )-H Bond Activation.

Direct alkylation of a methyl group, on di- and trisubstituted ureas, with terminal alkenes by C(sp3 )-H bond activation proceeded in the presence of a hydroxoiridium/bisphosphine catalyst to give high yields of the corresponding addition products. The hydroxoiridium/bisphosphine complex generates an amidoiridium intermediate by reaction with ureas having an N-H bond.

An N-terminal region of a Myb-like protein is involved in its intracellular localization and activation of a gibberellin-inducible proteinase gene in germinated rice seeds.

The expression of the gene for a proteinase (Rep1) is upregulated by gibberellins. The CAACTC regulatory element (CARE) of the Rep1 promoter is involved in the gibberellin response. We isolated a cDNA for a CARE-binding protein containing a Myb domain in its carboxyl-terminal region and designated the gene Carboxyl-terminal Myb1 (CTMyb1). This gene encodes two polypeptides of two distinctive lengths, CTMyb1L and CTMyb1S, which include or exclude 213 N-terminal amino acid residues, respectively. CTMyb1S transactivated the Rep1 promoter in the presence of OsGAMyb, but not CTMyb1L. We observed an interaction between CTMyb1S and the rice prolamin box-binding factor (RPBF). A bimolecular fluorescence complex analysis detected the CTMyb1S and RPBF complex in the nucleus, but not the CTMyb1L and RPBF complex. The results suggest that the arrangement of the transfactors is involved in gibberellin-inducible expression of Rep1.

Endoscopic drainage of orbital subperiosteal hematoma secondary to acute rhinosinusitis in a child.

Acute rhinosinusitis is frequently associated with secondary orbital infection, most commonly subperiosteal abscess. Although orbital subperiosteal abscess is a deadly disease that might lead to blind and cavernous sinus thrombosis, recent review of literature showed that immediate surgical intervention might not always be necessary for subperiosteal abscess. Orbital inflammation secondary to sinusitis is common in children, whereas orbital subperiosteal hematoma secondary to sinusitis is extremely rare, with only 11 reported cases, including one case in children. All the cases were treated with surgical intervention. Here we present a 12-year-old girl with rhinosinusitis and proptosis. Emergent endoscopic sinus surgery with partial removal of the lamina papyracea revealed dark brown fluid in the subperiosteal space. The patient was symptom-free 2 weeks after surgery. The present case was treated exclusively via an endonasal approach, whereas all 11 previous cases of subperiosteal hematoma were treated with external incision. The endonasal approach is favorable, especially for young female patients. Our review of literature shows that sudden onset, afebrile, and few signs of inflammation on blood test in patients with subperiosteal lesion may indicate subperiosteal hematoma. Surgery rather than antibiotic administration should be considered for the treatment of suspected subperiosteal hematoma. Treatment through only the endonasal approach is possible even if the hematoma is located in the roof of the orbit.

HDR syndrome, detected in the neonatal period by newborn hearing screening.

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.

Discovery and Hit to Lead Optimization of Macrocyclic Peptides as Novel Tropomyosin Receptor Kinase A Antagonists.

Tropomyosin receptor kinases (Trks) are receptor tyrosine kinases activated by neurotrophic factors, called neurotrophins. Among them, TrkA interacts with the nerve growth factor (NGF), which leads to pain induction. mRNA-display screening was carried out to discover a hit compound 2, which inhibits protein-protein interactions between TrkA and NGF. Subsequent structure optimization improving phosphorylation inhibitory activity and serum stability was pursued using a unique process that took advantage of the peptide being synthesized by translation from mRNA. This gave peptide 19, which showed an analgesic effect in a rat incisional pain model. The peptides described here can serve as a new class of analgesics, and the structure optimization methods reported provide a strategy for discovering new peptide drugs.

Formation of highly twisted ribbons in a carboxymethylcellulase gene-disrupted strain of a cellulose-producing bacterium.

Cellulases are enzymes that normally digest cellulose; however, some are known to play essential roles in cellulose biosynthesis. Although some endogenous cellulases of plants and cellulose-producing bacteria are reportedly involved in cellulose production, their functions in cellulose production are unknown. In this study, we demonstrated that disruption of the cellulase (carboxymethylcellulase) gene causes irregular packing of de novo-synthesized fibrils in Gluconacetobacter xylinus, a cellulose-producing bacterium. Cellulose production was remarkably reduced and small amounts of particulate material were accumulated in the culture of a cmcax-disrupted G. xylinus strain (F2-2). The particulate material was shown to contain cellulose by both solid-state (13)C nuclear magnetic resonance analysis and Fourier transform infrared spectroscopy analysis. Electron microscopy revealed that the cellulose fibrils produced by the F2-2 cells were highly twisted compared with those produced by control cells. This hypertwisting of the fibrils may reduce cellulose synthesis in the F2-2 strains.

Electrophysiological mapping of the cochlear nucleus with multi-channel bipolar surface microelectrodes.

Auditory potentials in response to electrical stimulation of the cochlear nucleus were recorded in guinea pigs using two types of multi-channel surface microelectrodes with inter-electrode distance of 100 and 200 µm. Unequivocal waves of electrically evoked auditory brainstem responses (EABRs), which increased in amplitude with increasing stimulation current, were consistently observed. Electrophysiological mapping with these multichannel electrodes could clearly distinguish stimulation points showing positive EABRs from points showing undetectable EABRs, indicating that multi-channel surface microelectrodes have great potential in clinical use to determine the optimal location for the positioning of auditory brainstem implants, and may allow more precise discrimination of pitch. Further study to clarify the optimal inter-electrode distance for humans is necessary before application to physiological mapping in the human cochlear nucleus.

Three-dimensional visualization of plant tissues and organs by X-ray micro-computed tomography.

Studies visualizing plant tissues and organs in three-dimension (3D) using micro-computed tomography (CT) published since approximately 2015 are reviewed. In this period, the number of publications in the field of plant sciences dealing with micro-CT has increased along with the development of high-performance lab-based micro-CT systems as well as the continuous development of cutting-edge technologies at synchrotron radiation facilities. The widespread use of commercially available lab-based micro-CT systems enabling phase-contrast imaging technique, which is suitable for the visualization of biological specimens composed of light elements, appears to have facilitated these studies. Unique features of the plant body, which are particularly utilized for the imaging of plant organs and tissues by micro-CT, are having functional air spaces and specialized cell walls, such as lignified ones. In this review, we briefly describe the basis of micro-CT technology first and then get down into details of its application in 3D visualization in plant sciences, which are categorized as follows: imaging of various organs, caryopses, seeds, other organs (reproductive organs, leaves, stems and petioles), various tissues (leaf venations, xylems, air-filled tissues, cell boundaries, cell walls), embolisms and root systems, hoping that wide users of microscopes and other imaging technologies will be interested also in micro-CT and obtain some hints for a deeper understanding of the structure of plant tissues and organs in 3D. Majority of the current morphological studies using micro-CT still appear to be at a qualitative level. Development of methodology for accurate 3D segmentation is needed for the transition of the studies from a qualitative level to a quantitative level in the future.

Examination of Factors Affecting the Likelihood of Whether Individuals Would Purchase Cartilage Conduction Hearing Aids.

Cartilage conduction hearing aids (CC-HAs) are a novel type of hearing aid relying on cartilage conduction, the so-called third auditory conduction pathway. However, CC-HAs have only recently entered routine clinical use, and therefore data on their usefulness are lacking. The purpose of this study was to examine the possibility of assessing whether individual patients would show good adaptation to CC-HAs. Thirty-three subjects (41 ears in total) underwent a free trial of CC-HAs. Age, disease category, and the pure-tone threshold of air and bone conduction, unaided field sound threshold, aided field sound threshold, and functional gain (FG) at 0.25, 0.5, 1, 2, and 4 kHz were compared between patients who subsequently purchased and did not purchase the CC-HAs. Overall, 65.9% of the subjects purchased CC-HAs after the trial. In comparison to non-purchasers, those who decided to purchase CC-HAs showed better pure tone hearing thresholds at high frequencies for both air conduction (2 and 4 kHz) and bone conduction (1, 2, and 4 kHz), as well as for aided thresholds in the sound field (1, 2, and 4 kHz) when using CC-HAs. Therefore, the high-frequency hearing thresholds of subjects trialing CC-HAs might be helpful for identifying those who are likely to benefit from them.

Demonstration of osmotically dependent promotion of aerenchyma formation at different levels in the primary roots of rice using a 'sandwich' method and X-ray computed tomography.

BACKGROUND AND AIMS: The effect of environmental factors on the regulation of aerenchyma formation in rice roots has been discussed for a long time, because aerenchyma is constitutively formed under aerated conditions. To elucidate this problem, a unique method has been developed that enables sensitive detection of differences in the development of aerenchyma under two different environmental conditions. The method is tested to determine whether aerenchyma development in rice roots is affected by osmotic stress. METHODS: To examine aerenchyma formation both with and without mannitol treatment in the same root, germinating rice (Oryza sativa) caryopses were sandwiched between two agar slabs, one of which contained 270 mm of mannitol. The roots were grown touching both slabs and were thereby exposed unilaterally to osmotic stress. As a non-invasive approach, refraction contrast X-ray computed tomography (CT) using a third-generation synchrotron facility, SPring-8 (Super photon ring 8 GeV, Japan Synchrotron Radiation Research Institute), was used to visualize the three-dimensional (3-D) intact structure of aerenchyma and its formation in situ in rice roots. The effects of unilateral mannitol treatment on the development of aerenchyma were quantitatively examined using conventional light microscopy. KEY RESULTS: Structural continuity of aerenchyma was clearly visualized in 3-D in the primary root of rice and in situ using X-ray CT. Light microscopy and X-ray CT showed that the development of aerenchyma was promoted on the mannitol-treated side of the root. Detailed light microscopic analysis of cross-sections cut along the root axis from the tip to the basal region demonstrated that aerenchyma developed significantly closer to the root tip on the mannitol-treated side of the root. CONCLUSIONS: Continuity of the aerenchyma along the rice root axis was morphologically demonstrated using X-ray CT. By using this 'sandwich' method it was shown that mannitol promoted aerenchyma formation in the primary roots of rice.

Iridium-Catalyzed Enantioselective Direct α-C-H Alkylation of Saturated Cyclic Amines with Alkenes.

Enantioselective direct α-C(sp3)-H alkylation of saturated cyclic amines having N-methylbenzimidazolyl as a directing group was realized by using a cationic iridium/chiral diphosphine catalyst. The alkylation of pyrrolidine derivatives with various terminal alkenes proceeded to give α-alkylated products in high yields with high enantioselectivities. Chiral α,α'-dialkylated pyrrolidine derivatives were also synthesized by using an excess of alkenes or by stepwise alkylation.

Hearing Outcomes of Transmastoid Plugging for Superior Canal Dehiscence Syndrome by Underwater Endoscopic Surgery: With Special Reference to Transient Bone Conduction Increase in Early Postoperative Period.

OBJECTIVE: To investigate the influence on hearing of transmastoid plugging of the superior semicircular canal accompanied with membranous superior canal transection by underwater endoscopic ear surgery (UWEES) for the superior semicircular canal dehiscence syndrome. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seven patients underwent plugging with membranous superior canal transection with UWEES from 2017 to 2019. INTERVENTION: Bone conduction (BC) thresholds (250, 500, 1000, 2000, 4000 Hz) were repetitively examined in early postoperative period. MAIN OUTCOME MEASURES: Subjective symptoms and pure-tone audiometry. RESULTS: Transient BC threshold increase was detected in all cases in early postoperative period and hearing levels were ameliorated in 1 to 2 months. The mean maximum BC threshold elevations (dB) during the early postoperative period (within 1 mo) and the postoperative stable hearing period (after 2 mo) were 18.6 and 2.9 at 250 Hz, 24.3 and 8.6 at 500 Hz, 26.4 and 8.6 at 1000 Hz, 28.6 and 7.1 at 2000 Hz, and 30.0 and 0.8 (except for scale-out cases) at 4000 Hz. respectively. The mean maximum BC thresholds in the early period were significantly elevated compared with those in the stable period at each frequency (p < 0.01). CONCLUSIONS: Hearing outcomes of transmastoid plugging with transection of the membranous superior canal by using UWEES were found favorable in a long-term follow-up. However, it caused transient reversible hearing loss in all cases. The BC increase in early postoperative period may not cause permanent hearing loss but improvement for the surgical technique may still be necessary.

Middle ear adenoma with facial palsy: A case report and a review of the literature.

A 52-year-old man presented to our emergency department with an acute onset of right-sided facial nerve (FN) palsy of House-Brackmann grade V. Electroneurography (ENoG) was conducted with no response at the right FN, as compared with the left FN (0%). We performed a biopsy of the right middle ear mass and histological studies showed the tumor to be neuroendocrine tumors (NET) of the middle ear. We resected the tumor with canal wall down mastoidectomy and reconstructed the posterior meatal wall with soft tissue. Three months after surgery, the FN paralysis had improved with House-Brackmann grade II. We reviewed cases of NET with FN palsy, and nine patients, including our case, have been reported. Our case is the first report of ENoG for the description of FN palsy due to NET. Although the ENoG value was 0%, it was remarkably improved by surgery. The other cases of NET patients with FN palsy also recovered FN function after surgery. These results suggest that it is recommended to perform the total resection of the tumor to improve the FN function.

Three-dimensionally visualized rhizoid system of moss, Physcomitrium patens, by refraction-contrast X-ray micro-computed tomography.

Land plants have two types of shoot-supporting systems, root system and rhizoid system, in vascular plants and bryophytes. However, since the evolutionary origin of the systems is different, how much they exploit common systems or distinct systems to architect their structures is largely unknown. To understand the regulatory mechanism of how bryophytes architect the rhizoid system responding to environmental factors, we have developed the methodology to visualize and quantitatively analyze the rhizoid system of the moss, Physcomitrium patens, in 3D. The rhizoids having a diameter of 21.3 µm on the average were visualized by refraction-contrast X-ray micro-computed tomography using coherent X-ray optics available at synchrotron radiation facility SPring-8. Three types of shape (ring-shape, line and black circle) observed in tomographic slices of specimens embedded in paraffin were confirmed to be the rhizoids by optical and electron microscopy. Comprehensive automatic segmentation of the rhizoids, which appeared in three different form types in tomograms, was tested by a method using a Canny edge detector or machine learning. The accuracy of output images was evaluated by comparing with the manually segmented ground truth images using measures such as F1 score and Intersection over Union, revealing that the automatic segmentation using machine learning was more effective than that using the Canny edge detector. Thus, machine learning-based skeletonized 3D model revealed quite dense distribution of rhizoids. We successfully visualized the moss rhizoid system in 3D for the first time.

Iridium-catalyzed enantioselective addition of an N-methyl C-H bond to α-trifluoromethylstyrenes via C-H activation.

The Ir-catalyzed enantioselective addition of an N-methyl C-H bond of 2-(methylamino)pyridine derivatives to α-trifluoromethylstyrenes proceeded via C-H activation to give chiral γ-branched amine derivatives having a trifluoromethyl-substituted stereocenter. It was found that a bulky and electron-withdrawing group at the 3-position of 2-(methylamino)pyridines was necessary for the present C-H addition reaction catalyzed by a cationic iridium/chiral bisphosphine complex.

Reconstruction using a free vascularised medial femoral condyle corticoperiosteal flap for osteomyelitis of the juxta-articular distal radius: A case report and literature review.

Osteomyelitis of the epiphysis after a distal radius fracture is uncommon. If not adequately and promptly treated, the detrimental effects on wrist function can be devastating. However, management of septic bone defects of the epiphysis is significantly challenging. We report the case of a patient with juxta-articular distal radius osteomyelitis successfully treated with a free vascularised corticoperiosteal flap from the medial femoral condyle (MFC corticoperiosteal flap). A 46-year-old right-handed man fell on the grass from a height of 2 m during a demolition. He was diagnosed with a right distal radius and ulnar styloid process fracture. He underwent open reduction and internal fixation. However, he developed a deep infection, resulting in postoperative osteomyelitis. Therefore, thorough debridement was performed and an external fixator was applied. Antibiotics were administered according to the culture results. He underwent reconstruction for bone defect using an MFC corticoperiosteal flap 28 days after re-operation. The patient could resume work without limitations 4 months after the reconstruction. The infection subsided completely, and radiographs confirmed bone union at 5 months after the reconstruction. His wrist range of motion was 40° in dorsal flexion (uninjured side 70°), 50° in palmar flexion (75°), 80° in supination (90°), and 90° in pronation (90°). There was no donor site complication. The patient has reported no pain for 1 year since the injury. The use of the MFC corticoperiosteal flap for reconstruction of the juxta-articular distal radius osteomyelitis decreased the time required for bone union, enabled local antibiotic delivery to control infection, and helped preserve wrist function.

Underwater Endoscopic Ear Surgery for Closure of Cholesteatomatous Labyrinthine Fistula With Preservation of Auditory Function.

OBJECTIVE: To analyze the outcomes of the underwater endoscopic ear surgery (UWEES) technique for closure of cholesteatomatous labyrinthine fistula (LF) with preservation of auditory function. STUDY DESIGN: Retrospective case review study. SETTING: Tertiary referral center. PATIENTS: A total of 12 patients with cholesteatomatous LF. INTERVENTION: Surgical method of closure using UWEES for cholesteatomatous LF to minimize inner ear damage. Artificial cerebrospinal fluid (CSF) was used as the perfusate, except for earlier cases when saline was employed. MAIN OUTCOME MEASURES: Comparison of bone conductance hearing level (BCHL) before and after surgery. A change of BCHL less than 10 dB was defined as successful preservation of bone conductance hearing. RESULTS: All cases of LF were treated successfully by closure using the UWEES technique. Seven cases were type I, one was type IIa, and four were type III according to the Milewski and Dornhoffer classification of LF. The average LF size was 3.1 mm (1-7 mm). Eleven patients were evaluated and their bone conductance hearing was well preserved in all of them (11/11). One patient was too young for preoperative evaluation of BCHL, but hearing preservation was verified 2 years later at the age of 6 years. Remarkably, none of the patients complained of vertigo, except for only a slight manifestation on postoperative day 1. CONCLUSION: The UWEES technique was effective for closure of cholesteatomatous LF with preservation of auditory function.