Structure of Full-Length SMC and Rearrangements Required for Chromosome Organization.

Multi-subunit SMC complexes control chromosome superstructure and promote chromosome disjunction, conceivably by actively translocating along DNA double helices. SMC subunits comprise an ABC ATPase "head" and a "hinge" dimerization domain connected by a 49 nm coiled-coil "arm." The heads undergo ATP-dependent engagement and disengagement to drive SMC action on the chromosome. Here, we elucidate the architecture of prokaryotic Smc dimers by high-throughput cysteine cross-linking and crystallography. Co-alignment of the Smc arms tightly closes the interarm space and misaligns the Smc head domains at the end of the rod by close apposition of their ABC signature motifs. Sandwiching of ATP molecules between Smc heads requires them to substantially tilt and translate relative to each other, thereby opening up the Smc arms. We show that this mechanochemical gating reaction regulates chromosome targeting and propose a mechanism for DNA translocation based on the merging of DNA loops upon closure of Smc arms.

Crystal structure of PYCH_01220 from Pyrococcus yayanosii potentially involved in binding nucleic acid.

We report the crystal structure of PYCH_01220, a hypothetical protein in Pyrococcus yayanosii CH1. This protein is composed of two domains, named Domain A and Domain B. While Domain B is not significantly homologous to known protein structures, Domain A is structurally analogous to the C-terminal ribonuclease domain of Escherichia coli colicin D. Domain A has a positively charged surface patch rendered by 13 basic residues, eight arginine or lysine residues of which are evolutionarily conserved. Electrophoretic mobility shift assays showed that PYCH_01220 binds to DNA, and charge-inversion mutations on this patch negatively affect the DNA binding, suggesting that the function of PYCH_01220 might involve nucleic acid-binding via the positively charged patch.

Nystagmus in Ramsay Hunt syndrome with or without dizziness.

BACKGROUND: The presence of dizziness has been reported as a negative prognostic factor for recovery of facial palsy in Ramsay Hunt syndrome (RHS). The aim of this study was to investigate the incidence and patterns of nystagmus in RHS patients without dizziness, and discuss possible mechanisms. We also compared the severity and prognosis of facial palsy between RHS patients with and without dizziness. METHODS: From January 2014 to January 2019, 36 patients diagnosed with RHS (27 with dizziness and 9 without dizziness) were included. Patterns of nystagmus were examined and categorized using video-nystagmography. House-Brackmann(HB) grade of facial palsy was compared between RHS patients with and without dizziness. RESULTS: Not only RHS patients with dizziness exhibited nystagmus in most cases (96%, 26 of 27) but also as many as 67% (6 of 9) of RHS patients without dizziness exhibited nystagmus, though the intensity was remarkably weak. In both groups of RHS with and without dizziness, direction-fixed nystagmus and direction-changing positional nystagmus were observed. Initial HB grade and recovery of facial palsy after treatment were not significantly different between RHS with and without dizziness. CONCLUSION: Various patterns of nystagmus including direction-fixed and positional direction-changing nystagmus were observed in RHS patients, and inflammation of the vestibular nerve and inner ear end organs may be responsible for the production of nystagmus in these patients. The results support that the evaluation of vestibular function may be necessary even in RHS patients who do not complain of dizziness or vertigo.

RNA activation-independent DNA targeting of the Type III CRISPR-Cas system by a Csm complex.

The CRISPR-Cas system is an adaptive and heritable immune response that destroys invading foreign nucleic acids. The effector complex of the Type III CRISPR-Cas system targets RNA and DNA in a transcription-coupled manner, but the exact mechanism of DNA targeting by this complex remains elusive. In this study, an effector Csm holocomplex derived from Thermococcus onnurineus is reconstituted with a minimalistic combination of Csm1121334151, and shows RNA targeting and RNA-activated single-stranded DNA (ssDNA) targeting activities. Unexpectedly, in the absence of an RNA transcript, it cleaves ssDNA containing a sequence complementary to the bound crRNA guide region in a manner dependent on the HD domain of the Csm1 subunit. This nuclease activity is blocked by a repeat tag found in the host CRISPR loci. The specific cleavage of ssDNA without a target RNA suggests a novel ssDNA targeting mechanism of the Type III system, which could facilitate the efficient and complete degradation of foreign nucleic acids.

Middle Ear Ceruminous Gland Adenoma Obstructing the Eustachian Tube Orifice.

Ceruminous glands are located in the skin of the cartilaginous portion of the external auditory canal, and ceruminous gland adenoma originating from the middle ear mucosa is extremely rare. We report a case of middle ear ceruminous gland adenoma which caused long-standing otomastoiditis and mixed hearing loss with a large air-bone gap by obstructing the bony Eustachian tube. We discuss the clinical characteristics and histologic features of the present case.

Bubbling tinnitus caused by change in head position.

Because the density of air is lower than the effusion, air bubbles can be passively moved by a head position change, causing a bubbling sound in the affected ear.

Positional Nystagmus after Acute Vertiginous Attack in Meniere's Disease.

There have been no reports regarding nystagmus observed immediately after the end of an acute vertiginous attack in patients with Meniere's disease. The aim of this study was to demonstrate positional direction-changing nystagmus in patients with Meniere's disease, and to discuss the mechanism that underlies this nystagmus. Video-nystagmography was recorded in two patients with definite Meniere's disease, who showed positional direction-changing nystagmus during the period immediately after a vertigo attack. In one patient, video-nystagmographic recording was conducted 5 h after an episode of vertigo attack, and it showed very weak, persistent positional geotropic direction-changing nystagmus. In the other patient, video-nystagmographic recording was conducted 23 h after an episode of vertigo attack, and it showed very weak, persistent positional apogeotropic direction-changing nystagmus. Our patients exhibited very weak, persistent positional direction-changing nystagmus, which was geotropic in one and apogeotropic in the other. This type of positional nystagmus has been reported in other inner ear disorders and it cannot be clearly explained by typical benign paroxysmal positional vertigo. The change in chemical composition and/or electrolyte concentration of the inner ear fluid, although still unclear, may underlie the production of this characteristic nystagmus in these patients.

Immediate and short-term effects of Gufoni and Appiani liberatory maneuver for treatment of ageotropic horizontal canal benign paroxysmal positional vertigo: A prospective randomized trial.

OBJECTIVE: To examine the treatment effects of repositioning maneuvers with the head turned 45° downwards (Gufoni maneuver) and 45° upwards (Appiani maneuver) in 25 patients with ageotropic horizontal semicircular canal (HSCC) benign paroxysmal positional vertigo (BPPV). METHODS: Patients were randomly assigned to the Gufoni or Appiani maneuvers, and their immediate and short-term efficacy was investigated. RESULTS: The immediate treatment response was successful in four of 16 patients who were treated with the Appiani maneuver and were not successful in any of the nine patients treated with the Gufoni maneuver. The patients who showed spontaneous resolution during follow-up outnumbered the patients who showed resolution of ageotropic HSCC BPPV immediately after the repositioning maneuvers. CONCLUSION: This study showed a very low immediate resolution rate of ageotropic HSCC BPPV after the Gufoni maneuver; this may be attributed to the less effectiveness of the Gufoni maneuver against debris that often exists in the canal side of the cupula. Another interesting finding was that the rate of spontaneous resolution during the follow-up period was higher than that of immediate resolution after the repositioning maneuvers, which may support the recently proposed hypothesis that ageotropic positional nystagmus can also be evoked by causes other than the otolithic attachment on the cupula, such as a slight change in the biochemical composition of the inner ear fluids. LEVEL OF EVIDENCE: 3.

Effects of Olfactory Training in Patients With Postinfectious Olfactory Dysfunction.

OBJECTIVES: Postinfectious olfactory dysfunction (PIOD) is the most common etiology of olfactory dysfunction, and olfactory training (OT) is an accepted treatment modality for PIOD. Some studies have investigated OT in Korean patients, but they involved odorants unfamiliar to Koreans or had no control group. The aim of this study was to verify the efficacy of OT in PIOD patients, using odorants familiar to Koreans and including a control group. METHODS: We enrolled a total of 104 Korean patients with PIOD over the 3-year study period. All participants were assessed using endoscopy and an olfactory function test at the baseline assessment and 3 months after OT. The olfactory function test was performed using the Korean version of Sniffin' stick (KVSS) II. Nasal and psychological function was evaluated using a visual analog scale and the Mini-Mental State Examination. OT was performed over a period of 3 months, using five odorants (rose, lemon, cinnamon, orange, and peach). RESULTS: OT improved olfactory function in approximately 40% of subjects over a period of 12 weeks compared to non-OT subjects. A comparison of changes between the initial and follow-up assessments demonstrated that the OT group had significantly better olfactory results for the total KVSS II, threshold, and identification scores than the non-OT group. The degree of olfactory improvement after OT was affected by the initial score. CONCLUSION: The effects of OT in patients with PIOD were demonstrated in this study. A meaningful contribution of this study is that Korean patients were tested using odors familiar to them in comparison with a control group.