A PTHrP Gradient Drives Mandibular Condylar Chondrogenesis via Runx2.

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone-related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the growing mandibular condyle. In the postnatal MCC of PthrpmCherry/+ mice, PTHrP-mCherry was specifically expressed by cells in the superficial layer immediately adjacent to RUNX2-expressing cells in the polymorphic layer. PTHrP ligands diffused across the polymorphic and chondrocyte layers where its cognate receptor PTH1R was abundantly expressed. We further analyzed the mandibular condyle of PthrpmCherry/mCherry mice lacking functional PTHrP protein (PTHrP-KO). At embryonic day (E) 18.5, the condylar process and MCC were significantly truncated in the PTHrP-KO mandible, which was associated with a significant reduction in cell proliferation across the polymorphic layer and a loss of SOX9+ cells in the chondrocyte layers. The PTHrP-KO MCC showed a transient increase in the number of Col10a1+ hypertrophic chondrocytes at E15.5, followed by a significant loss of these cells at E18.5, indicating that superficial layer-derived PTHrP prevents premature chondrocyte exhaustion in the MCC. The expression of Runx2, but not Sp7, was significantly reduced in the polymorphic layer of the PTHrP-KO MCC. Therefore, PTHrP released from cells in the superficial layer directly acts on cells in the polymorphic layer to promote proliferation of chondrocyte precursor cells and prevent their premature differentiation by maintaining Runx2 expression, revealing a unique PTHrP gradient-directed mechanism that regulates MCC chondrogenesis.

Multipole polaron in the devil's staircase of CeSb.

Rare-earth intermetallic compounds exhibit rich phenomena induced by the interplay between localized f orbitals and conduction electrons. However, since the energy scale of the crystal-electric-field splitting is only a few millielectronvolts, the nature of the mobile electrons accompanied by collective crystal-electric-field excitations has not been unveiled. Here, we examine the low-energy electronic structures of CeSb through the anomalous magnetostructural transitions below the Néel temperature, ~17 K, termed the 'devil's staircase', using laser angle-resolved photoemission, Raman and neutron scattering spectroscopies. We report another type of electron-boson coupling between mobile electrons and quadrupole crystal-electric-field excitations of the 4f orbitals, which renormalizes the Sb 5p band prominently, yielding a kink at a very low energy (~7 meV). This coupling strength is strong and exhibits anomalous step-like enhancement during the devil's staircase transition, unveiling a new type of quasiparticle, named the 'multipole polaron', comprising a mobile electron dressed with a cloud of the quadrupole crystal-electric-field polarization.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection. We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gµ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models. Additionally, we develop and test a third model that interpolates between these two models. Our results improve upon the previous LIGO-Virgo constraints on Gµ by 1 to 2 orders of magnitude depending on the model that is tested. In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gµâ‰²4×10^{-15}. In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models.

Association between forest and greenspace walking and stress-coping skills among workers of Tsukuba Science City, Japan: A cross-sectional study.

Objectives: Recently, "sense of coherence" (SOC) as a concept of stress-coping, has been gaining considerable attention. Although many studies have investigated the factors related to strong SOC, we found little evidence about the associations between SOC and habits that are easy to perform in everyday life. The aim our study was to examine the prevalence of workers who engage in forest walking and greenspace walking and examine their association with SOC score. Study design: A cross-sectional study. Methods: An anonymous, self-report web questionnaire was conducted in November 2017. The study population included 19481 workers belonging to the Tsukuba Science City Network and data of 6466 participants (3965 men and 2501 women) were analyzed. Results: The percentage of participants who engage in forest and greenspace walking at least once a year were 55.9% and 75.9%, respectively. Associations between forest/greenspace walking and SOC score were calculated using Chi-squared tests. Multinomial logistic regression analyses with SOC score group (strong/middle/weak) as a dependent variable and forest/greenspace walking as explanatory variables were performed. Statistically significant positive associations were observed between strong SOC and those who engaged in forest/greenspace walking after adjusting for socioeconomic factors. The odds ratios for strong SOC were 3.65 (95% CI â€‹= â€‹1.70-7.85) for forest walking at least once a week and 2.12 for greenspace walking (95% CI â€‹= â€‹1.54-2.92) at least once a week. Conclusions: Our findings suggested that forest/greenspace walking may enhance workers' stress-coping skills.

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star-black hole, and binary black hole systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. During O3, the median localization volume (90% credible region) is expected to be on the order of 10 5 , 10 6 , 10 7 Mpc 3 for binary neutron star, neutron star-black hole, and binary black hole systems, respectively. The localization volume in O4 is expected to be about a factor two smaller than in O3. We predict a detection count of 1 - 1 + 12 ( 10 - 10 + 52 ) for binary neutron star mergers, of 0 - 0 + 19 ( 1 - 1 + 91 ) for neutron star-black hole mergers, and 17 - 11 + 22 ( 79 - 44 + 89 ) for binary black hole mergers in a one-calendar-year observing run of the HLV network during O3 (HLVK network during O4). We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers.

Devil's staircase transition of the electronic structures in CeSb.

Solids with competing interactions often undergo complex phase transitions with a variety of long-periodic modulations. Among such transition, devil's staircase is the most complex phenomenon, and for it, CeSb is the most famous material, where a number of the distinct phases with long-periodic magnetostructures sequentially appear below the Néel temperature. An evolution of the low-energy electronic structure going through the devil's staircase is of special interest, which has, however, been elusive so far despite 40 years of intense research. Here, we use bulk-sensitive angle-resolved photoemission spectroscopy and reveal the devil's staircase transition of the electronic structures. The magnetic reconstruction dramatically alters the band dispersions at each transition. Moreover, we find that the well-defined band picture largely collapses around the Fermi energy under the long-periodic modulation of the transitional phase, while it recovers at the transition into the lowest-temperature ground state. Our data provide the first direct evidence for a significant reorganization of the electronic structures and spectral functions occurring during the devil's staircase.

Candida auris: A pathogen difficult to identify, treat, and eradicate and its characteristics in Japanese strains.

Candida auris is a multidrug-resistant and emergent pathogen that has caused healthcare-associated infection outbreaks. Recently, C. auris has spread worldwide; nevertheless, it was unexpectedly rare before 2009. Based on the molecular epidemiological analysis, C. auris may independently emerge at specific areas at first and recently may be transmitted to other continents. As C. auris cannot be detected using conventional methods, internally transcribed spacers, D1/D2 regions of the 26S rDNA sequencing, and/or matrix-assisted laser desorption ionization time-of-flight mass spectrometry method can be selected as comparatively accessible choices. Thus, detection of C. auris using the conventional method might be underestimated. In Japan, all C. auris strains were isolated from ear specimen and not from invasive mycoses. Japan strains were classified as an East Asian clade under a single clone. Although colonization, virulence, and infection pattern are almost the same as with other Candida species, its antifungal resistance is different. Fluconazole resistance is notably common, but resistance to all three classes of antifungals (azole, polyene, and echinocandin) rarely exists. Once C. auris is detected, screening, emphasis on hand hygiene adherence, use of single-patient room isolation, contact precaution, surveillance, and eradication from the environment and patients are appropriately required for infection control.

Cross-Sectional Inverse Association of Regular Soy Intake with Insulin Resistance in Japanese Elderly.

Levels of isoflavones, biomarkers of soy intake, in 24-hour urine (24U) were inversely related to coronary heart disease (CHD) mortality in the World Health Organization's Cardiovascular Disease and Alimentary Comparison Study. Considering 24 U isoflavone levels were highest and CHD mortality was lowest in the Japanese, who maintained the world's longest life expectancy, the association of regular soy intake with cardiometabolic risk was investigated in Japanese adults (20-49 years old) and elderly (50-79 years old). In multivariate analysis adjusted for age, sex, and drug treatments, mean 24 U isoflavone excretion was significantly inversely associated with insulin resistance in the elderly and significantly associated with blood folate and potassium in the elderly, but also positively associated with 24 U salt in the elderly. These findings indicate that low-salt soy should be recommended to improve glucose metabolism in elderly Japanese.

Maximizing T c by tuning nematicity and magnetism in FeSe1-x S x superconductors.

A fundamental issue concerning iron-based superconductivity is the roles of electronic nematicity and magnetism in realising high transition temperature (T c). To address this issue, FeSe is a key material, as it exhibits a unique pressure phase diagram involving non-magnetic nematic and pressure-induced antiferromagnetic ordered phases. However, as these two phases in FeSe have considerable overlap, how each order affects superconductivity remains perplexing. Here we construct the three-dimensional electronic phase diagram, temperature (T) against pressure (P) and isovalent S-substitution (x), for FeSe1-x S x . By simultaneously tuning chemical and physical pressures, against which the chalcogen height shows a contrasting variation, we achieve a complete separation of nematic and antiferromagnetic phases. In between, an extended non-magnetic tetragonal phase emerges, where T c shows a striking enhancement. The completed phase diagram uncovers that high-T c superconductivity lies near both ends of the dome-shaped antiferromagnetic phase, whereas T c remains low near the nematic critical point.

Overexpression of bone morphogenetic protein-3b (BMP-3b) in adipose tissues protects against high-fat diet-induced obesity.

BACKGROUND: Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-ß superfamily and has several activities that differ from those of other BMPs. We previously found that BMP-3b is highly expressed in adipocytes, its level is increased during obesity, and it inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ (PPARγ) in vitro. However, the function of BMP-3b in adipose tissues in vivo remains unknown. METHODS: To determine the role of BMP-3b overexpression in adipose tissues in vivo, we generated transgenic mice (BMP-3b Tg) by using a conditional overexpression approach in fatty acid-binding protein 4-expressing adipocytes. We examined BMP-3b Tg mice fed a high-fat diet to elucidate the effects of BMP-3b on obesity. Adipocyte function was evaluated as expression of adipogenic and lipogenic markers in adipose tissue. We also performed glucose and insulin tolerance tests (GTT and ITT, respectively), and biochemical analysis of serum and measured energy expenditure by indirect calorimetry. RESULTS: BMP-3b Tg mice fed a high-fat diet showed decreases in weight gain, fat-pad mass and adipocyte area, compared with wild-type mice. The adipose tissues of BMP-3b Tg mice showed downregulated expression of PPARγ and its target gene encoding fatty acid translocase/CD36. In addition, BMP-3b Tg mice had decreased blood glucose levels on GTT and ITT, and their serum leptin levels were decreased and adiponectin concentrations were increased. These changes in BMP-3b Tg mice were accompanied by increased energy expenditure, indicated as increased locomotor activity and oxygen consumption. CONCLUSIONS: These results provide in vivo evidence that BMP-3b regulates adipocyte function to cause an anti-obesity effect.

Dietary Intake Is Associated with Occlusal Force Rather Than Number of Teeth in 80-y-Old Japanese.

There has been a growing interest in the association between the number of teeth and dietary intake in older populations. However, people around the age of 80 y have frequently lost most of their teeth, and dental prostheses replacing the missing teeth play an important role in masticatory function. Therefore, masticatory function cannot be evaluated by the number of teeth alone. The occlusal force of the complete dental arches is an index of masticatory function, reflecting not only the number of teeth, but the effect of removable dentures. The purpose of this cross-sectional study was to determine the relative importance of the number of teeth and occlusal force in association with dietary intake in 80-y-old Japanese people. This study included 760 community-dwelling Japanese people aged 79 y to 81 y. The authors measured bilateral maximal occlusal force in the intercuspal position using pressure-sensitive sheets. Removable denture wearers kept their dentures in place during the measurements. Energy-adjusted food groups and nutrient intake during the preceding month were assessed by a brief self-administered diet history questionnaire. The authors assessed linear trends in food and nutrient intake in relation to the number of teeth and occlusal force after adjusting for gender and socioeconomic status (education level, financial status, family structure, resident area and BMI). P values of < 0.05 were considered to be statistically significant. The authors found that the number of teeth was not associated with the energy-adjusted intake of any food group examined. In contrast, a decline in occlusal force was significantly associated with a lower intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most vitamins and minerals ( P for trend < 0.05). We conclude that food and nutrient intake was more closely associated with occlusal force than the number of teeth in community-dwelling Japanese people aged 79 y to 81 y. Knowledge Transfer Statement: This cross-sectional study of older Japanese people showed that, after controlling for considerable covariates, occlusal force rather than the number of teeth is positively associated with energy-adjusted intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most of vitamins and minerals. This means that reduced occlusal force may unconsciously lead older people toward a habitual unhealthy dietary intake. Older people have frequently lost most of their teeth and require prosthetics to restore masticatory function. Bilateral occlusal force is therefore a better measure of masticatory function than the number of remaining teeth. Our findings suggest that prosthetic rehabilitation is a significant factor in the prevention and management of chronic diseases and frailty through better dietary intake in older populations.

Longitudinal study of factors affecting taste sense decline in old-old individuals.

The sense of taste plays a pivotal role for personal assessment of the nutritional value, safety and quality of foods. Although it is commonly recognised that taste sensitivity decreases with age, alterations in that sensitivity over time in an old-old population have not been previously reported. Furthermore, no known studies utilised comprehensive variables regarding taste changes and related factors for assessments. Here, we report novel findings from a 3-year longitudinal study model aimed to elucidate taste sensitivity decline and its related factors in old-old individuals. We utilised 621 subjects aged 79-81 years who participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians Study for baseline assessments performed in 2011 and 2012, and then conducted follow-up assessments 3 years later in 328 of those. Assessment of general health, an oral examination and determination of taste sensitivity were performed for each. We also evaluated cognitive function using Montreal Cognitive Assessment findings, then excluded from analysis those with a score lower than 20 in order to secure the validity and reliability of the subjects' answers. Contributing variables were selected using univariate analysis, then analysed with multivariate logistic regression analysis. We found that males showed significantly greater declines in taste sensitivity for sweet and sour tastes than females. Additionally, subjects with lower cognitive scores showed a significantly greater taste decrease for salty in multivariate analysis. In conclusion, our longitudinal study revealed that gender and cognitive status are major factors affecting taste sensitivity in geriatric individuals.

Arthroscopic decompression with indigo carmine for treating paralabral cysts in the shoulder.

Paralabral cysts in the shoulder are a relatively rare pathology. It is sometimes difficult to detect the location of a paralabral cyst in the shoulder using arthroscopy, and it can be difficult to confirm sufficient decompression by arthroscopy. We describe the case of a 64-year-old woman who underwent arthroscopic decompression for a paralabral cyst in the shoulder. Indigo carmine was injected into the cyst under ultrasonography guidance just before the operation. The leakage point of indigo carmine was detected using arthroscopy. Arthroscopic decompression was performed until the indigo carmine was completely discharged. Her shoulder pain, limited range of motion, and muscle weakness during abduction and external rotation improved postoperatively. Magnetic resonance imaging confirmed the disappearance of the cyst. Arthroscopic decompression using an ultrasonography-guided injection of indigo carmine is a useful treatment for a paralabral cyst in the shoulder.

Factors related to taste sensitivity in elderly: cross-sectional findings from SONIC study.

The sense of taste is important, as it allows for assessment of nutritional value, as well as safety and quality of foods, with several factors suggested to be associated with taste sensitivity. However, comprehensive variables regarding taste and related factors have not been utilised in previous studies for assessments of sensitivity. In the present study, we performed cross-sectional analyses of taste sensitivity and related factors in geriatric individuals who participated in the SONIC Study. We analysed 2 groups divided by age, 69-71 years (young-old, n = 687) and 79-81 years (old-old, n = 621), and performed a general health assessment, an oral examination and determination of taste sensitivity. Contributing variables were selected by univariate analysis and then subjected to multivariate logistic regression analysis. In both groups, females showed significantly better sensitivity for bitter and sour tastes. Additionally, higher cognitive scores for subjects with a fine taste for salty were commonly seen in both groups, while smoking, drinking, hypertension, number of teeth, stimulated salivary flow salt intake and years of education were also shown to be associated with taste sensitivity. We found gender and cognitive status to be major factors affecting taste sensitivity in geriatric individuals.

Long-term detection of seasonal influenza RNA in faeces and intestine.

Some cases of seasonal influenza virus (human influenza A virus (IAV)/human influenza B virus (IBV)) are associated with abdominal symptoms. Although virus RNA has been detected in faeces, intestinal infection has not been clearly demonstrated. We aimed to provide evidence that IAV/IBV infects the human intestine. This prospective observational study measured virus RNA in faecal and sputum samples from 22 patients infected with IAV/IBV (19 IAV positive and three IBV positive). Nineteen patients were included in the analysis and were assigned to faecal IAV-positive and -negative groups. Virus kinetics were examined in faecal samples from an IAV-infected patient (patient 1) and an IBV-infected patient (patient 2). Finally, intestinal tissue from an IAV-diagnosed patient who developed haemorrhagic colitis and underwent colonoscopy was examined for the presence of replicating IAV (patient 3). Virus RNA was detected in faecal samples from 8/22 IAV/IBV-infected patients (36.4%). Diarrhoea occurred significantly more often in the faecal IAV-positive group (p 0.002). In patients 1 and 2, virus RNA became undetectable in sputum on days 7 and 10 after infection, respectively, but was detected in faeces for a further 2 weeks. Virus mRNA and antigens were detected in intestinal tissues (mucosal epithelium of the sigmoid colon) from patient 3. These findings suggest that IAV/IBV infects within the intestinal tract; thus, the human intestine may be an additional target organ for IAV/IBV infection.