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Here, we tested the hypothesis that tensile and compressive stresses generated in the alveolar bone proper regulate site-specific cellular and functional changes in osteoclasts and osteoblasts. Thirty-two 13-week-old male mice were randomly divided into four groups: two experimental groups with vertical loading obliquely from the palatal side to the buccal side of the maxillary molar (0.9 N) 30 min per day for 8 or 15 days and unloaded controls (n = 8). Calcein and alizarin were administered 8 and 2 days before euthanization, respectively, to detect the time of bone formation. Undecalcified sections parallel to the occlusal plane were prepared on the palatal root and the surrounding alveolar bone in the middle of the root length. The alveolar perimeter was divided into 12 equal regions for site analysis, and the bone histomorphometric parameters were obtained for each region. Data from in vivo microfocus computed tomography were used to construct animal-specific finite element models. 2D stress distribution images were overlain on histology images obtained from the same location. Significant differences in the total perimeter between groups and between loading and unloading in each region were statistically analyzed (α = 0.05). Osteoclast counts and the alizarin label ratio were significantly higher in the loaded group than in the unloaded group in regions where the maximum von Mises and principal tensile stresses were the highest along the perimeter. The label ratio of calcein was significantly lower in the 8-day loaded group than in the unloaded group, indicating that the calcein-labeled surface was resorbed by osteoclasts that appeared during the loading period. The effect of loading was mitigated by an increase in the maximum principal compressive stress. We conclude that bone resorption and bone formation are functions of site-specific tension and compression in the alveolar bone proper, confirming our hypothesis. This finding is critical for the advancement of diagnosis and treatment planning in clinical dentistry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Memory-related neuronal responses are often elicited by sensory stimuli that recapitulate previous experience. Despite the importance of this sensory input processing, its underlying mechanisms remain poorly understood. Caenorhabditis elegans chemotax towards salt concentrations experienced in the presence of food. The amphid sensory neurons ASE-left and ASE-right respond to increases and decreases of ambient salt concentration in opposite manners. AIA, AIB and AIY interneurons are post-synaptic to the ASE pair and are thought to be involved in the processing of salt information transmitted from ASE. However, it remains elusive how the responses of these interneurons are regulated by stimulus patterns. Here we show that AIY interneurons display an experience-dependent response to gradual salt concentration changes but not to abrupt stepwise concentration changes. Animals with AIY intact (but AIA and AIB ablated) chemotax towards low salt concentrations similarly to wild-type animals after cultivation with low salt. ASE neurons transmit salt information about the environment through glutamatergic signaling, directing the activity of the interneurons AIY that promote movement towards favorable conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Japan Neuroscience Society and Elsevier Ltd. All rights reserved.)

Objective: Exercise training is recommended for its possible favorable effects on Fontan pathophysiology. This study aimed to elucidate the impact of pediatric exercise capacity trajectory, which may mimic the effect of exercise training, on late adult Fontan pathophysiology., Methods: Since 1990, 97 Fontan patients had consecutively undergone two serial cardiopulmonary exercise tests (CPX1 and CPX2) during childhood (ages 8 ± 2 and 14 ± 2 years) and one during adulthood (CPX3; age 23 ± 5 years). The changes in peak oxygen uptake (PVO 2 : % of normal value) from CPX1 to CPX2 (1-dPVO 2 ) and from CPX2 to CPX3 (2-dPVO 2 ) were calculated, and then the patients were divided into four subgroups according the 1-dPVO 2 and 2-dPVO 2 ., Results: In their adulthood, when compared with groups with negative 1-dPVO 2 , the central venous pressure, plasma brain natriuretic peptide level, and renal resistive index were lower, whereas liver synthetic function, body fat-free percentage, and PVO 2 were higher in those with positive 1-dPVO 2 (p < 0.05-0.0001). However, these favorable associations of 2-d-PVO 2 with adult Fontan pathophysiology were not observed, except for the PVO 2 . After CPX3, 13 unexpected events occurred, and the risk was 76% lower in the groups having positive 1-dPVO 2 than in those with negative 1-dPVO 2 (hazard ratio, 0.24; 95% confidence interval, 0.09-0.62; p = 0.0035)., Conclusions: A positive exercise capacity trajectory during childhood predicts better adult Fontan pathophysiology, including better prognosis. Thus, prescription of exercise could be a promising strategy in the management of pediatric Fontan patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: A subset of patients undergoing cardiac resynchronization therapy (CRT) for heart failure (HF) with severe left ventricular (LV) dysfunction experience only short-lived LV reverse remodeling. Little is known about the incidence and prognosis of this finding. We sought to identify predictors of a brief response and investigated the prognosis in a retrospective study., Methods: A total of 528 patients from a Japanese multicenter database with full echocardiography datasets were enrolled. Follow-up was 3.4±1.3years. Based on relative reduction in LV end-systolic volume (LVESV) at 6months, we categorized patients as responders (reduction in LVESV ≥15%) and non-responders (NRs; reduction in LVESV <15%). Based on reduction in LVESV at 1-2years, responders were subdivided into long-lasting responders (reduction in LVESV ≥15%) and brief responders (reduction in LVESV <15%)., Results: Of 328 responders, 50 (15%) were brief responders. Predictors of brief response were prior ventricular tachyarrhythmia, a non-left bundle-branch block (LBBB) intrinsic QRS pattern, and prior hospitalization for HF. The risk of all-cause death in brief responders was significantly lower than that in NRs (P=0.034) and tended to be higher than that in long-lasting responders (P=0.080)., Conclusions: Approximately 15% of responders were brief responders. Prior ventricular tachyarrhythmia, a non-LBBB pattern, and HF hospitalization were independent predictors of a brief response. Brief response was significantly associated with decreased risk of all-cause death compared with NRs and had a tendency toward increased risk of all-cause death compared with long-lasting responders., (Copyright © 2017 Elsevier B.V. All rights reserved.)

It is known that protein malnutrition develops fatty liver in rats. However, the mechanisms by which protein malnutrition enhances lipid accumulation in the liver are not fully understood. Our previous studies have demonstrated that protein malnutrition upregulates insulin signaling with an increase in TG levels in rat livers. Here, we examined whether the upregulated insulin signaling contributes to an enhancement of TG accumulation under protein malnutrition. As it is difficult to analyze insulin-induced hepatic TG synthesis in vivo, the isolated hepatocytes derived from rats fed a low-protein diet were used. The hepatocytes were isolated from rats fed a 15% casein diet (15C) as a control diet or a 5% casein diet (5C) as a low-protein diet and then treated with insulin. As shown in vivo, insulin signaling was upregulated in isolated hepatocytes from 5C-fed rats (5C hepatocytes). However, the insulin-induced increase in the mRNA levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS), was similar in both groups. The amounts of TG synthesized from both glucose and palmitate, as well as ACC1 and FAS protein levels, were increased at the basal state in 5C hepatocytes, but were not further increased by insulin. These results indicate that TG synthesis via both de novo fatty acid synthesis and esterification is enhanced in 5C hepatocytes, which is independent of the upregulation of insulin signaling., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the relationship between the change of language symptoms and the change of regional cerebral blood flow (rCBF) in the recovery process of two children with acquired aphasia caused by infarctions from Moyamoya disease with an onset age of 8years., Methods: We compared the results for the Standard Language Test of Aphasia (SLTA) with rCBF changes in 7 language regions in the left hemisphere and their homologous regions in the right hemisphere at 4 time points from 3weeks for up to 5years after the onset of aphasia, while controlling for the effect of age., Results: In both cases, strong correlations were seen within a hemisphere between adjacent regions or regions that are connected by neuronal fibers, and between some language regions in the left hemisphere and their homologous regions in the right hemisphere. Conversely, there were differences between the two cases in the time course of rCBF changes during their recovery process., Conclusion: Consistent with previous studies, the current study suggested that both hemispheres were involved in the long-term recovery of language symptoms in children with acquired aphasia. We suggest that the differences between both cases during their recovery process might be influenced by the brain states before aphasia, by which hemisphere was affected, and by the timing of the surgical revascularization procedure. However, the changes were observed in the data obtained for rCBF with strong correlations with the changes in language performance, so it is possible that rCBF could be used as a biomarker for language symptom changes., (Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study is to analyze the impact of average contact force (CF) and its regional variability during pulmonary vein isolation (PVI) for atrial fibrillation (AF) on periprocedural parameters and midterm outcome., Methods: This retrospective cohort study enrolled 57 drug-refractory AF patients who underwent initial PVI for AF using an open-irrigated CF catheter (SmartTouch Thermocool, Biosense Webster, Diamond Bar, CA, USA). Thirty patients were assigned to a lower CF (LCF) group (average CF≤10g) and 27 patients to a higher CF (HCF) group (average CF>10g). The relationship between CF and clinical outcome was analyzed., Results: Patients were followed-up for 317±57 days after PVI. The CF was 8.1±1.3g in the LCF group and 12.4±1.5g in the HCF group. Higher average CF was associated with shorter ablation time (28±6min vs. 36±9min, p=0.0002) and lower radiofrequency energy delivery (79±18 vs. 99±26, p=0.0016) for PVI. The rate of acute PV reconnection (APVR) was similar in both groups (LCF group 60% vs. HCF group 44%, p=0.36). Four patients (13%) in the LCF group and nine patients (33%) in the HCF group experienced AF-recurrence. Average CF did not impact on AF-recurrence during midterm clinical outcome (p=0.09 by log-rank test). In the non-recurrence group (n=44), average CF was higher at left posterosuperior PV and right anteroinferior PV than that in the recurrence group (n=13) (p=0.012 and p=0.004, respectively)., Conclusions: Higher average CF decreased ablation time and radiofrequency energy delivery for PVI, but did not decrease APVR rate or improve midterm clinical outcome., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to evaluate the association between left atrial (LA) structural remodeling and very late recurrence [VLR; initial recurrence >12 months after catheter ablation (CA)] after successful CA for non-paroxysmal atrial fibrillation (AF)., Methods: We retrospectively evaluated 63 patients who underwent initial, single ablation for drug-refractory persistent or long-standing persistent AF and those who had no recurrence in the first year after CA. We followed patients for a mean of 3.2±1.5 years and divided them into VLR and no-recurrence (NR) groups. Before and 3 months after ablation, all patients were subjected to 64-slice multidetector computed tomography scanning to estimate LA volume, including maximum and minimum volume during the cardiac cycle (LAMaxV and LAMinV, respectively), and the LA emptying fraction., Results: VLR occurred in 21 patients. The reduction rate of LAMaxV after CA was significantly larger in the NR group than in the VLR group (25±19% vs. 5±18%, p=0.0002). Receiver operating characteristic analysis was performed to determine the best cut-off values in the prediction of VLR. The highest area-under curve was obtained with post-CA LAMinV [0.828 (95% confidence interval, 0.712-0.912), p<0.0001], with a best cut-off value of 44mL (sensitivity 81.0%, specificity 81.0%)., Conclusions: Persistent LA structural remodeling after initially successful CA for non-paroxysmal AF may be an important risk factor for VLR., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

A disintegrin and metalloproteases (ADAMs) are a family of proteins that have been reported to be involved in several inflammatory conditions. We examined the secretion of ADAM-10 in biological fluids from patients with rheumatoid arthritis (RA) and the role it plays in monocyte migration. ADAM-10 levels were measured using enzyme-linked immunosorbent assays and immunofluorescence. To examine the role of ADAM-10 in RA synovial fluids (SFs), we studied THP-1 (human acute monocyte leukemia cell line) and monocyte chemotaxis. To determine whether ADAM-10 plays a role in cell proliferation in the RA synovium, we assayed the proliferation of ADAM-10 small interfering RNA (siRNA)-transfected RA fibroblast-like synoviocytes (FLSs). The ADAM-10 level in RA serum was significantly higher than that in normal serum and was correlated with a disease activity score of 28. ADAM-10-depleted RA SFs showed a decrease in THP-1 and monocyte migratory activity compared with that of sham-depleted controls. ADAM-10 siRNA inhibited monocyte adhesion to RA FLSs. Finally, blocking ADAM-10 secretion in RA FLSs resulted in decreased production of fractalkine/CX3CL1 and vascular endothelial cell growth factor. These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method of decreasing inflammation and potentially treating other inflammatory diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A 63-year-old woman with a past history of right subdural hematoma (SDH) at the age of 61 years was referred to our hospital under a suspicion of aceruloplasminemia (ACP). A neurological examination revealed very mild cognitive impairment and cerebellar ataxia. Blood chemistry data showed deficient ceruloplasmin (Cp), decreased copper, and increased ferritin. A nonsense mutation (c.2630G>A, p.Trp858Ter) was detected in the Cp gene. Brain magnetic resonance imaging (MRI) showed marked hypointensity at the surface of the cerebrum, cerebellum, and brainstem bilaterally, in addition to the bilateral basal ganglia, thalamus, and dentate nucleus, suggesting the coexistence of ACP and superficial siderosis (SS). The characteristics of SS in ACP have not been examined neuroradiologically or neuropathologically in great detail, while SDH and its curative surgery are known to cause SS. The distribution of the hypointensity areas on MRI was expanded bilaterally to the subtentorial areas of this patient, which was much more widespread than observed in typical SS after SDH. We speculate that the underlying ACP may expand the SS induced by SDH. Cp would accelerate iron export from the brain via the blood-cerebrospinal fluid (CSF) barrier, or CSF-brain barrier when excessive iron is loaded into the subarachnoid space., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aspergillus oryzae is a fungus that is used widely in traditional Japanese fermentation industries. In this study, the lethal and mutagenic effects of different linear energy transfer (LET) radiation in freeze-dried conidia of A. oryzae were investigated. The lethal effect, which was evaluated by a 90% lethal dose, was dependent on the LET value of the ionizing radiation. The most lethal ionizing radiation among that tested was (12)C(5+) ion beams with an LET of 121keV/μm. The (12)C(5+) ion beams had a 3.6-times higher lethal effect than low-LET (0.2keV/μm) γ-rays. The mutagenic effect was evaluated by the frequency of selenate resistant mutants. (12)C(6+) ion beams with an LET of 86keV/μm were the most effective in inducing selenate resistance. The mutant frequency following exposure to (12)C(6+) ion beams increased with an increase in dose and reached 3.47×10(-3) at 700Gy. In the dose range from 0 to 700Gy, (12)C(5+) ion beams were the second most effective in inducing selenate resistance, the mutant frequency of which reached a maximum peak (1.67×10(-3)) at 400Gy. To elucidate the characteristics of mutation induced by ionizing radiation, mutations in the sulphate permease gene (sB) and ATP sulfurylase gene (sC) loci, the loss of function of which results in a selenate resistant phenotype, were compared between (12)C(5+) ion beams and γ-rays. We detected all types of transversions and transitions. For frameshifts, the frequency of a +1 frameshift was the highest in all cases. Although the incidence of deletions >2bp was generally low, deletions >20bp were characteristic for (12)C(5+) ion beams. γ-rays had a tendency to generate mutants carrying a multitude of mutations in the same locus. Both forms of radiation also induced genome-wide large-scale mutations including chromosome rearrangements and large deletions. These results provide new basic insights into the mutation breeding of A. oryzae using ionizing radiation., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)

A 78-year-old cachectic woman who previously had repair of atrial septal defect was admitted to the hospital for congestive heart failure. Cardiac workup revealed chronic constrictive pericarditis; no evidence of coronary or valvular disease was found. She underwent corrective surgery for pericardiectomy. Intraoperative transesophageal echocardiography after pericardiectomy demonstrated acute development of severe mitral regurgitation, which was not preoperatively observed. She eventually required mitral valve replacement and tricuspid valve repair after conservative management failed. She recovered from the operation and was discharged. We believe that this is the first report of successful surgical management of mitral regurgitation that developed acutely after pericardiectomy.

Background: The therapeutic potential of using stem cells is tremendous. Mesenchymal stromal cells (MSC) have now been isolated in various tissues including bone marrow (BM), muscle, skin and adipose tissue. Among them, adipose tissue could be one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity and abundance of stem cells. The large numbers of stem cells in adipose tissue means that clinically relevant stem cell numbers could be extracted from the tissue, potentially eliminating the need for in vitro expansion. To utilize these characteristics of adipose tissue fully, Cytori Therapeutics Inc. has developed a closed system called Celution to isolate and concentrate stem cells and regenerative cells automatically from adipose tissue., Methods: Adipose tissue-derived cells were isolated using the Celution system. The output from the Celution was characterized using multicolor FACS analysis with CD31, CD34, CD45, CD90, CD105 and CD146. The multidifferentiation potential of the cells was analyzed using adipogenic and osteogenic media., Results: Our results showed that cells from the Celution are composed of heterogeneous cell populations including adipose-derived stem cells (ASC) (CD31- CD34+ CD45- CD90+ CD105- CD146-), endothelial (progenitor) cells (CD31+ CD34+ CD45- CD90+ CD105- CD146+) and vascular smooth muscle cells (CD31- CD34+ CD45- CD90+ CD105- CD146+). We also confirmed the output contains cells able to differentiate into adipogenic and osteogenic phenotypes. Our results show that cells isolated with the Celution and manually are equivalent., Discussion: Cells from adipose tissue can be processed by Celution within the time frame of a single surgical procedure. This system could provide a 'real-time' treatment setting that is cost-effective and safe.

PTEN is a dual protein and lipid phosphatase that dephosphorylates PIP3 at the 3' position, thereby antagonizing PI3-kinase activity. A reduction in PI3' kinase activity enhances the susceptibility of cells to apoptosis. By stably transfecting PC12 cells with an antisense PTEN construct, endogenous PTEN protein levels were reduced by approximately 50% and etoposide-induced apoptosis was markedly decreased. Furthermore, IGF-I receptor abrogation of this apoptotic effect was inhibited by both PI3' kinase and by specific inhibitors of p38 MAP kinase. Thus, we show for the first time that p38 MAP kinase is involved in this process.

PAL31 is a nuclear protein expressed by various cell types. In the present study, the expression and function of PAL31 were examined in the cytokine-regulated growth of T and B cell lines. Treatment of the cells with mitogens [ovine PRL, recombinant rat placental lactogen-I (PL-I) and human IL-3] caused a dose-dependent increase in the expression of PAL31 mRNA in the PRL-dependent cell line Nb2, and IL-3 dependent cell line BaF3. A time-course study on synchronized Nb2 cells revealed that the expression of PAL31 is specific to the late G1 and S phases. Immunocytological studies revealed that PAL31 accumulates in the nuclei at the S phase. Furthermore, the antisense oligonucleotide for PAL31 severely inhibited the proliferation of Nb2 cells by inhibiting cells progressing to the S phase. Thus, PAL31 is a nuclear protein associated with cell cycle progression., (Copyright 2001 Academic Press.)

We cloned a cDNA encoding a novel protein (PAL31) predominantly expressed in the fetal rat brain by differential display. PAL31 contains leucine-rich repeat domains, a highly acidic region and a putative nuclear localization signal. PAL31 has 50-70% similarity to SSP29, APRIL, LANP, PHAP I, and PP32. Expression of PAL31 mRNA in the brain was high during the fetal period and decreased after birth. Immunohistochemical studies showed that PAL31 is expressed in the entire embryonic brain, whereas in the adult brain its expression is restricted to the subventricular zone where there are neural progenitor cells. It was also revealed that PAL31 is colocalized with PCNA in the nucleus, indicating that the PAL31 expression is developmentally regulated. Considering the primary structure of PAL31 and its spatiotemporal expression pattern, PAL31 is a novel nuclear protein related to the development of the brain through the proliferation of neuronal cells., (Copyright 2000 Academic Press.)

Lewy body (LB) is consistently found in the substantia nigra in Parkinson's disease. We report a 68-year-old woman with late-onset, dopa-responsive parkinsonism. Her parents were first cousins, but no other affected individuals were present in the family. Autopsy revealed moderate loss of pigmented neurons with gliosis, but neither LBs nor neurofibrillary tangles in the substantia nigra. The locus ceruleus showed neuronal loss with scarce LBs. The most striking change was found in the dorsal vagal nucleus, where marked neuronal loss and fibrillary gliosis with many LBs were evident. Despite the use of ubiquitin and alpha-synuclein immunohistochemistry, no further LBs were identified in other brain regions. These findings suggest that this case was an unusual, anatomically restricted manifestation of LB disease.

To understand the underlying mechanism of force generation by myosin motor, it is crucial to know which part of the molecule is essential for the process. Recent structure determination of myosin motor domain at atomic resolution has revealed that the domain comprises two smaller domains, the "ATPase domain" consisting of only an N-terminal segment of the heavy chain and the "neck domain" consisting of a long alpha-helix of the heavy chain and two light chains. This atomic structure begs the question of whether both domains are required for force generation. To answer it, we genetically truncated the head to generate a recombinant fragment composed of the "ATPase domain" alone. The truncated head drove sliding movement of actin filaments and generated force in a novel in vitro assay system, which allows us to hold a specific site of the head on a glass surface. These results indicate that the compact ATPase domain functions as a force-generating machinery of the myosin motor.

This paper presents the 7-year follow-up of successful replantation in a patient whose right leg was amputated. The patient's daily activities surpass those that would have otherwise been attained by the use of an artificial leg. The authors believe that this patient is one of the most successful cases of replantation of the leg, with a long follow-up period.