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The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb interphalangeal joint, including the stalk of the cyst. The skin incision varies for cases depending upon the geometry. We propose a surgical method utilizing blind lateral approaches for treating such mucous cysts.

The transposition of an adjacent finger following the loss of a finger due to a malignant tumor resection improves hand function. However, patients may not accept the resulting appearance of a three-finger hand. A 28-year-old male with a malignant fibroblastic tumor at the base of the ring finger underwent resection of the tumor, excising the phalanx and a portion of the metacarpal. He refused a ray amputation and subsequent fifth-finger transposition. Therefore, we reconstructed the defect with a long-vascularized subtotal second toe from the metacarpal neck to the middle phalanx base of the fourth finger. There was no tumor recurrence, and the patient was highly satisfied with hand function and cosmetic appearance at 3 years of follow-up.

The recurrence risk of estrogen receptor (ER)-positive breast cancer remains high for a long period of time, unlike other types of cancer. Late recurrence reflects the ability of cancer cells to remain dormant through various events, including cancer stemness acquisition, but the detailed mechanism is unknown. ESR1 locus enhancing and activating noncoding RNAs (ELEANORS) are a cluster of nuclear noncoding RNAs originally identified in a recurrent breast cancer cell model. Although their functions as chromatin regulators in vitro are well characterized, their roles in vivo remain elusive. In this study, we evaluated the clinicopathologic features of ELEANORS, using primary and corresponding metastatic breast cancer tissues. The ELEANOR expression was restricted to ER-positive cases and well-correlated with the ER and progesterone receptor expression levels, especially at the metastatic sites. ELEANORS were detected in both primary and metastatic tumors (32% and 29%, respectively), and frequently in postmenopausal cases. Interestingly, after surgery, patients with ELEANOR-positive primary tumors showed increased relapse rates after, but not within, 5 years. Multivariate analysis showed that ELEANORS are an independent recurrence risk factor. Consistently, analyses with cell lines, mouse xenografts, and patient tissues revealed that ELEANORS upregulate a breast cancer stemness gene, CD44, and maintain the cancer stem cell population, which could facilitate tumor dormancy. Our findings highlight a new role of nuclear long noncoding RNAs and their clinical potential as predictive biomarkers and therapeutic targets for late recurrence of ER-positive breast cancer.

Trinucleotide repeat sequences (TRSs), consisting of 10 unique classes of repeats in DNA, are members of microsatellites and abundantly and non-randomly distributed in many eukaryotic genomes. The lengths of TRSs are mutable, and the expansions of several TRSs are implicated in hereditary neurological diseases. However, the underlying causes of the biased distribution and the dynamic properties of TRSs in the genome remain elusive. Here, we examined the effects of TRSs on nucleosome formation in vivo by histone H4–S47C site-directed chemical cleavages, using well-defined yeast minichromosomes in which each of the ten TRS classes resided in the central region of a positioned nucleosome. We showed that (AAT)12 and (ACT)12 act as strong nucleosome-promoting sequences, while (AGG)12 and (CCG)12 act as nucleosome-excluding sequences in vivo. The local histone binding affinity scores support the idea that nucleosome formation in TRSs, except for (AGG)12, is mainly determined by the affinity for the histone octamers. Overall, our study presents a framework for understanding the nucleosome-forming abilities of TRSs.

Objective: Venous leg ulcers (VLUs) caused by chronic venous insufficiency are difficult to treat. Outcomes after compression therapy and the current standard of care often used in conjunction with other options vary widely. We examined the effects of foam inserts on sub-bandage pressures in patients with VLUs and compared use of foam inserts in elastic and inelastic compression bandaging. Methods: Six patients (≥20 years old) with VLUs and skin perfusion pressure >40 mmHg were included. Each patient underwent weekly treatment regimens of debridement, dressing changes, and dual sponge-insert application followed by elastic (n=3) or inelastic (n=3) compression bandaging. The median resting sub-bandage pressures of the ulcer beds, wound sizes, and healing percentages were recorded. Wound beds were biopsied before and after treatment for histological assessment. Nine healthy volunteers served as controls during preliminary testing. Results: With proper sub-bandage pressures (>35 mmHg), the average healing time was 88.0±66 days, which was shorter than anticipated (i.e., ≥6 months). Combining large and local sponge-foam inserts increased sub-bandage pressures regardless of the compression bandage selected, with marked improvements seen in deeper wounds. Conclusion: Layering one or two sponge-foam inserts beneath compression bandages facilitates uniform and optimal wound-bed pressure, which accelerates the healing of VLUs.

In eukaryotes, chromosome ends (telomeres) are tethered to the inner nuclear membrane. During the early stages of meiosis, telomeres move along the nuclear membrane and gather near the spindle-pole body, resulting in a bouquet-like arrangement of chromosomes. This chromosomal configuration appears to be widely conserved among eukaryotes, and is assumed to play an important role in the normal progression of meiosis, by mediating the proper pairing of homologous chromosomes. In fission yeast, the Bqt1-Bqt2 protein complex plays a key role in tethering the telomere to the inner nuclear membrane. However, the structural details of the complex required to clarify how telomeres are gathered near the spindle-pole body remain enigmatic. Previously, we devised a preparation procedure for the Schizosaccharomyces japonicus Bqt1-Bqt2 complex, in which a SUMO tag was fused to the N-terminus of the Bqt1 protein. This allowed us to purify the Bqt1-Bqt2 complex from the soluble fraction. In the present study, we found that a maltose-binding protein homolog, Athe_0614, served as a better fusion partner than the SUMO protein, resulting in the marked increase in the solubility of the Bqt1-Bqt2 complex. The Athe_0614 fusion partner may open up new avenues for X-ray crystallographic analyses of the structure of the Bqt1-Bqt2 complex.

While micronuclei (MN) store extranuclear DNA and cause genome instability, the effects of nuclear envelope (NE) assembly defects associated with MN on genome instability remain largely unknown. Here, we investigated the NE protein distribution in MN using HeLa human cervical cancer cells. Under the standard condition and two pharmacological culture conditions, we found that three types of NE protein assemblies were associated with MN: 1) intact NE assembly, in which both core and non-core NE proteins were evenly present; 2) type I assembly, in which only core NE proteins were detectable; and 3) type II assembly in which a region deficient for both core and non-core NE proteins existed and a pattern recognition receptor, cyclic guanosine monophos-phate-adenosine monophosphate synthase, was frequently detected. Our findings provide experimental settings and a method of grouping MN-associated NE defects, which may be helpful for researchers who are interested in regulation of genome and nuclear organization relevant to cancer development.

The fungal pathogen Candida albicans is surrounded by a cell wall that is the target of caspofungin and other echinocandin antifungals. Candida albicans can grow in several morphological forms, notably budding yeast and hyphae. Yeast and hyphal forms differ in cell wall composition, leading us to hypothesize that there may be distinct genes required for yeast and hyphal responses to caspofungin. Mutants in 27 genes reported previously to be caspofungin hypersensitive under yeast growth conditions were all caspofungin hypersensitive under hyphal growth conditions as well. However, a screen of mutants defective in transcription factor genes revealed that Cup9 is required for normal caspofungin tolerance under hyphal and not yeast growth conditions. In a hyphal-defective efg1Δ/Δ background, Cup9 is still required for normal caspofungin tolerance. This result argues that Cup9 function is related to growth conditions rather than cell morphology. RNA-seq conducted under hyphal growth conditions indicated that 361 genes were up-regulated and 145 genes were down-regulated in response to caspofungin treatment. Both classes of caspofungin-responsive genes were enriched for cell wall-related proteins, as expected for a response to disruption of cell wall integrity and biosynthesis. The cup9Δ/Δ mutant, treated with caspofungin, had reduced RNA levels of 40 caspofungin up-regulated genes, and had increased RNA levels of 8 caspofungin down-regulated genes, an indication that Cup9 has a narrow rather than global role in the cell wall integrity response. Five Cup9-activated surface-protein genes have roles in cell wall integrity, based on mutant analysis published previously (PGA31 and IFF11) or shown here (ORF19.3499, ORF19.851, or PGA28), and therefore may explain the hypersensitivity of the cup9Δ/Δmutant to caspofungin. Our findings define Cup9 as a new determinant of caspofungin susceptibility.

A technique to produce spin orientation in RI beams was developed for measurements of nuclear moments. The present scheme of two-step reaction realized highly spin-aligned RI beams for a wide range of exotic nuclei. Recently the two-step reaction scheme was applied to the magnetic moment measurement of an isomeric state of a neutron-rich nucleus 75Cu, where its magnetic moment was determined for the first time owing to a 30%-spin-aligned beam. A further perspective of the nuclear moment measurements employing the present scheme is expected.

In the near future, when designing and using Double Wall Airfoils, which will be manufactured by 3D printers, the positional relationship between the impingement cooling nozzle and the heat transfer enhancement ribs on the target plate naturally becomes more accurate. Taking these circumstances into account, an experimental study was conducted to enhance the heat transfer of the wall jet region of a round impingement jet cooling system. This was done by installing circular ribs or vortex generators (VGs) in the impingement cooling wall jet region. The local heat transfer coefficient was measured using the naphthalene sublimation method, which utilizes the analogy between heat and mass transfer. As a result, it was clarified that, within the ranges of geometries and Reynolds numbers at which the experiments were conducted, it is possible to improve the averaged Nusselt number Nu up to 21% for circular ribs and up to 51% for VGs.

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |μ|=2.31(14)μ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

In the nucleus, genomic DNA is wrapped around histone octamers to form nucleosomes. In principle, nucleosomes are substantial barriers to transcriptional activities. Nuclear non-coding RNAs (ncRNAs) are proposed to function in chromatin conformation modulation and transcriptional regulation. However, it remains unclear how ncRNAs affect the nucleosome structure. Eleanors are clusters of ncRNAs that accumulate around the estrogen receptor-α (ESR1) gene locus in long-term estrogen deprivation (LTED) breast cancer cells, and markedly enhance the transcription of the ESR1 gene. Here we detected nucleosome depletion around the transcription site of Eleanor2, the most highly expressed Eleanor in the LTED cells. We found that the purified Eleanor2 RNA fragment drastically destabilized the nucleosome in vitro. This activity was also exerted by other ncRNAs, but not by poly(U) RNA or DNA. The RNA-mediated nucleosome destabilization may be a common feature among natural nuclear RNAs, and may function in transcription regulation in chromatin., The Eleanor cluster of non-coding RNAs is localised upstream of estrogen receptor-α (ESR1) gene locus in estrogen-deprived breast cancer cells. Fujita et al find that RNA fragments of Eleanor2 and of other non-coding RNAs are able to destabilise nucleosomes in vitro, suggesting a role in transcriptional regulation.

In eukaryotes, genomic DNA is packaged into the nucleus together with histone proteins, forming chromatin. The fundamental repeating unit of chromatin is the nucleosome, a naturally symmetric structure that wraps DNA and is the substrate for numerous regulatory post-translational modifications. However, the biological significance of nucleosomal symmetry until recently had been unexplored. To investigate this issue, we developed an obligate pair of histone H3 heterodimers, a novel genetic tool that allowed us to modulate modification sites on individual H3 molecules within nucleosomes in vivo. We used these constructs for molecular genetic studies, for example demonstrating that H3K36 methylation on a single H3 molecule per nucleosome in vivo is sufficient to restrain cryptic transcription. We also used asymmetric nucleosomes for mass spectrometric analysis of dependency relationships among histone modifications. Furthermore, we extended this system to the centromeric H3 isoform (Cse4/CENP-A), gaining insights into centromeric nucleosomal symmetry and structure. In this review, we summarize our findings and discuss the utility of this novel approach.

We report on the operation of co-located ${}^{129}$Xe and ${}^{131}$Xe nuclear spin masers with an external feedback scheme, and discuss the use of ${}^{131}$Xe as a comagnetometer in measurements of the ${}^{129}$Xe spin precession frequency. By applying a correction based on the observed change in the ${}^{131}$Xe frequency, the frequency instability due to magnetic field and cell temperature drifts are eliminated by two orders of magnitude. The frequency precision of 6.2 $\mu$Hz is obtained for a 10$^4$ s averaging time, suggesting the possibility of future improvement to $\approx$ 1 nHz by improving the signal-to-noise ratio of the observation., Comment: 8 pages, 5 figures

Tensile residual stresses combined with an applied tensile stress can reduce the reliability of steel components. Nondestructive evaluation of residual stress is thus important to avoid unintended fatigue or cracking. Because magnetic hysteresis properties of ferromagnetic materials are sensitive to stress, nondestructive evaluation of residual stress through magnetic properties can be expected. The spatial mapping of local magnetic hysteresis properties becomes possible by using the acoustically stimulated electromagnetic (ASEM) method and the tensile stress dependence of the hysteresis properties has been investigated in steel. It is found that the coercivity H c and the remanent magnetization signal V r monotonically decrease with increasing the tensile stress. In this work, we verified the detection of residual stresses through the ASEM response in a welded steel plate. Tensile stresses are intentionally introduced on the opposite side of the partially welded face by controlling welding temperatures. We found that H c and V r clearly decrease in the welded region, suggesting that the presence of tensile residual stresses is well detected by the hysteresis parameters.

Time-dependent electron-nuclear wave functions of H2 were described by the floating Gaussian method. The equations of motion for the parameters that specify the wave functions are explicitly derived. By the imaginary time propagation, the ground-state wave functions were obtained. Five high frequency components appearing in the Fourier transformed spectra of the squared inter-particle distances were ascribed to the motion of electrons, and the two lowest frequency components among the five were identified as those representing coupling of the motions of electrons and nuclei.

Nucleosome-depleted regions (NDRs) (also called nucleosome-free regions or NFRs) are often found in the promoter regions of many yeast genes, and are formed by multiple mechanisms, including the binding of activators and enhancers, the actions of chromatin remodeling complexes, and the specific DNA sequences themselves. However, it remains unclear whether NDR formation per se is essential for transcriptional activation. Here, we examined the relationship between nucleosome organization and gene expression using a defined yeast reporter system, consisting of the CYC1 minimal core promoter and the lacZ gene. We introduced simple repeated sequences that should be either incorporated in nucleosomes or excluded from nucleosomes in the site upstream of the TATA boxes. The (CTG) 12 , (GAA) 12 and (TGTAGG) 6 inserts were incorporated into a positioned nucleosome in the core promoter region, and did not affect the reporter gene expression. In contrast, the insertion of (CGG) 12 , (TTAGGG) 6 , (A) 34 or (CG) 8 induced lacZ expression by 10–20 fold. Nucleosome mapping analyses revealed that the inserts that induced the reporter gene expression prevented nucleosome formation, and created an NDR upstream of the TATA boxes. Thus, our results demonstrated that NDR formation dictated by DNA sequences is sufficient for transcriptional activation from the core promoter in vivo .

We describe the present status of future high-precision measurements of nuclear g-factors utilizing laser-microwave double and laser-microwave-rf triple resonance methods for online-trapped, laser-cooled radioactive beryllium isotope ions. These methods have applicability to other suitably chosen isotopes and for beryllium show promise in deducing the hyperfine anomaly of 11Be with a sufficiently high precision to study the nuclear magnetization distribution of this one-neutron halo nucleus in a nuclear-model-independent manner.

Summary: Dermatofibrosarcoma protuberans (DFSP) is a slow-growing superficial sarcoma. Due to its high late local recurrence, thin skin graft is usually recommended for reconstruction after resection of the tumor. In this report, we present a case of giant DFSP in the groin region of young woman. Reconstruction of large groin defect after DFSP resection was performed by “split-skin paddle anterolateral thigh flap” instead of skin graft considering that the patient was a 29-year-old woman. This method enabled the primary closure of the donor site and provided the positive functional and esthetic outcomes. In the present case, the surgical scar is less conspicuous and the patient can climb and descend stairs without any trouble at 4 years after the surgery. With careful monitoring of the tumor recurrence, this technique may become a reliable reconstruction option for patients with large groin defect after resection of the malignant tumor.

Nucleosomes contain two copies of each core histone, held together by a naturally symmetric, homodimeric histone H3-H3 interface. This symmetry has complicated efforts to determine the regulatory potential of this architecture. Through molecular design and in vivo selection, we recently generated obligately heterodimeric H3s, providing a powerful tool for discovery of the degree to which nucleosome symmetry regulates chromosomal functions in living cells (Ichikawa et al., 2017). We now have extended this tool to the centromeric H3 isoform (Cse4/CENP-A) in budding yeast. These studies indicate that a single Cse4 N- or C-terminal extension per pair of Cse4 molecules is sufficient for kinetochore function, and validate previous experiments indicating that an octameric centromeric nucleosome is required for viability in this organism. These data also support the generality of the H3 asymmetric interface for probing general questions in chromatin biology.

Nucleosomes are the fundamental unit of eukaryotic chromosome packaging, comprised of 147 bp of DNA wrapped around two molecules of each of the core histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis of symmetry centered on the homodimeric interaction between the C-termini of the H3 molecules. To explore the functional consequences of nucleosome symmetry, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, allowing us to compare cells with single or double H3 alterations. Our biochemical validation of the heterodimeric X-Y interaction included intra-nucleosomal H3 crosslinking using dimethyl suberimidate (DMS). Here, we provide a detailed protocol for the use of DMS to analyze yeast nucleosomes.

We demonstrate spin-exchange optical pumping of 129Xe atoms with our newly made laser system. The new laser system was prepared to provide higher laser power required for the stable operation of spin maser oscillations in the 129Xe EDM experiment. We studied the optimum cell temperature and pumping laser power to improve the degree of 129Xe spin polarization. The best performance was achieved at the cell temperature of 100 ◦C with the presently available laser power of 1 W. The results show that a more intense laser is required for further improvement of the spin polarization at higher cell temperatures in our experiment.

Recently the “dispersion-matching two-step projectile-fragmentation (PF) method” has been developed as a new spin manipulation technique for a quantum system called a radioactive isotope (RI) beam [1]. This method obtains an RI beam with a high production yield while producing universally high spin alignment for a large variety of RIs. A proof-of-principle experiment was performed at the RIKEN RIBF facility [2]. By applying this method, it is expected that the measurement of the nuclear moment of an unstable nucleus, which was previously impossible, can be accomplished. In this article, after discussing the conventional mechanism for producing a spin orientation, the principle of the new method, demonstration experiments, evaluations based on the results of these experiments, and future prospects are described.

Telomeres are DNA-protein complexes located at the ends of linear eukaryotic chromosomes, and are essential for chromosome stability and maintenance. In most organisms, telomeres consist of tandemly repeated sequences of guanine-clusters. In higher eukaryotes, most of the telomeric repeat regions are tightly packaged into nucleosomes, even though telomeric repeats act as nucleosome-disfavoring sequences. Although telomeres were considered to be condensed heterochromatin structures, recent studies revealed that the chromatin structures in telomeres are actually dynamic. The dynamic properties of telomeric chromatin are considered to be important for the structural changes between the euchromatic and heterochromatic states during the cell cycle and in cellular differentiation. We propose that the nucleosome-disfavoring property of telomeric repeats is a crucial determinant for the lability of telomeric nucleosomes, and provides a platform for chromatin dynamics in telomeres. Furthermore, we discuss the influences of telomeric components on the nucleosome organization and chromatin dynamics in telomeres.

Micrococcal nuclease (MNase) has been widely used for analyses of nucleosome locations in many organisms. However, due to its sequence preference, the interpretations of the positions and occupancies of nucleosomes using MNase have remained controversial. Next-generation sequencing (NGS) has also been utilized for analyses of MNase-digests, but some technical biases are commonly present in the NGS experiments. Here, we established a gel-based method to map nucleosome positions in Saccharomyces cerevisiae, using isolated nuclei as the substrate for the histone H4 S47C-site-directed chemical cleavage in parallel with MNase digestion. The parallel mapping allowed us to compare the chemically and enzymatically cleaved sites by indirect end-labeling and primer extension mapping, and thus we could determine the nucleosome positions and the sizes of the nucleosome-free regions (or nucleosome-depleted regions) more accurately, as compared to nucleosome mapping by MNase alone. The analysis also revealed that the structural features of the nucleosomes flanked by the nucleosome-free region were different from those within regularly arrayed nucleosomes, showing that the structures and dynamics of individual nucleosomes strongly depend on their locations. Moreover, we demonstrated that the parallel mapping results were generally consistent with the previous genome-wide chemical mapping and MNase-Seq results. Thus, the gel-based parallel mapping will be useful for the analysis of a specific locus under various conditions.

Supplemental Digital Content is available in the text., Summary: Takotsubo cardiomyopathy (TCM) is a form of transient heart failure that clinically mimics acute coronary syndrome and is characterized by left ventricular wall motion abnormalities. The pathophysiology of TCM is not well established. TCM is often preceded by emotional or physical stress and may occur after surgery. We present 3 cases of TCM occurring after head and neck reconstructive surgery. Echocardiography plays a central role in the diagnosis of TCM. Left ventricular wall motion abnormalities extend beyond the territory of a single coronary artery. Coronary angiography and cardiac computed tomography can demonstrate the absence of coronary atherosclerosis and are useful for confirming the diagnosis of TCM. Particularly after reconstructive surgery, it is necessary to carefully monitor fluid replacement to avoid dehydration, which may compromise flap blood flow, although congestive heart failure is the most common complication of TCM. It is important to encourage ambulation as soon as possible, while considering the degree of cardiac impairment.

Co-magnetometry enables the elimination of systematic errors arising from the long-term drift in the magnetic field, and is essential for a precision measurement of spin precession frequency in experiments searching for electric dipole moment (EDM). $^{131}$Xe nuclear spin maser shows great promise as a co-magnetometer in a Xe EDM experiment, because the systematic error originating from the Xe-Rb interaction, which virtually limits the sensitivity in a case of a $^3$He co-magnetometer, will be cancelled out. The performance of a cell which contains both $^{129}$Xe and $^{131}$Xe was investigated. In the best cell among those fabricated this time, the signal-to-noise ratio in a free induction decay experiment turned out to be large enough for the operation as co-existing $^{129}$Xe-$^{131}$Xe masers.

Traditional “magic numbers” were once regarded as immutable throughout the nuclear chart. However, unexpected changes were found for unstable nuclei around N = 20. With both proton and neutron numbers around the magic number of 20, the neutron-rich 39Cl isotope provides a good test case for the study of the quantum-state evolution across the major shell. In the present work, the negative parity states in 39Cl are investigated through the β decay spectroscopy of 39S. Newly observed γ transitions together with a new state are assigned into the level scheme of 39Cl. The spin parity of 5/2− for the lowest negative parity state in 39Cl is reconfirmed using the combined γ transition information. These systematic observations of the negative parity states in 39Cl allow a comprehensive comparison with the theoretical descriptions. The lowest 5/2− state in 39Cl remains exotic in terms of comparisons with existing theoretical calculations and with the neighboring isotopes having similar single-particle configurations. Further experimental and theoretical investigations are suggested.

Summary:. Perifascial areolar tissue (PAT) is a loose connective tissue on deep fascia, such as on the groin, thigh, or temporal region, which has abundant vascular plexus and mesenchymal stem cells. Nonvascularized PAT grafts can survive even on hypovascular wound beds. Therefore, PAT grafting is a possible alternative to conventional flap surgery to cover exposed bone or artifacts. In this article, we describe 2 cases of PAT grafting for the treatment of skin ulcers with exposed bone and artificial plate after mandible reconstruction. After negative-pressure wound therapy, PAT was used to covering exposed artificial plate for both cases, and a skin graft onto the PAT graft was performed in 1 case. The ulcers improved in both cases without recurrence. The gold-standard treatment of intractable ulcers and fistulas with an exposed tendon, bone, or artifact is coverage by a well-vascularized skin flap. However, PAT grafting has advantages in similar situations, occasionally together with skin grafting and/or negative-pressure wound therapy, because it is technically simple and less invasive.