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Evidence on polypharmacy in patients with sarcopenia is lacking. We aimed to examine the association of polypharmacy with swallowing function and nutritional risk in post-stroke patient with sarcopenia. This retrospective cohort study included hospitalized patients diagnosed with sarcopenia who needed convalescent rehabilitation following stroke onset. Study outcomes were the Food Intake Level Scale (FILS) as dysphagia assessment and geriatric nutritional risk index (GNRI) as nutritional status at hospital discharge, respectively. To examine the impact of admission polypharmacy, multivariate linear regression analyses were used to determine whether the number of drugs prescribed at hospital admission was associated with these outcomes. As a result, of the 586 patients enrolled, 257 (mean age 79.3 years, 44.0% male) were diagnosed with sarcopenia and were finally analyzed high admission drug prescription numbers were independently associated with FILS (β = −0.133, p = 0.017) and GNRI (β = −0.145, p = 0.003) at hospital discharge, respectively. Polypharmacy is associated with dysphagia and malnutrition in post-stroke patients with sarcopenia. In addition to the combination of nutritional and exercise therapies, review and optimization of prescription medications may be warranted to treat sarcopenia in order to maximize improvement in outcomes for these patients.

To investigate the effect of trunk and appendicular skeletal muscle mass on the swallowing function at discharge in acute stroke patients.This retrospective cohort study included patients hospitalized after acute strokes. Skeletal muscle mass was measured by bioelectrical impedance analysis within 5 days of admission. The primary outcome was swallowing function at acute hospital discharge, assessed using the Functional Oral Intake Scale (FOIS). Secondary outcomes were Functional Independence Measure-eating (FIM-eating) scores and length of hospital stay.Data from 231 patients (age 72.2 years; 151 men) were included in the analysis. The median trunk muscle mass index (TMI) was 8.2 and 6.8 kg/mSkeletal muscle mass had site-specific impacts on swallowing function and eating activities. This finding may contribute to the design of more individualized rehabilitation programs.

sd1-d originating from 'Dee-geo-woo-gen' has been utilized to develop short-culmed indica varieties adaptable to higher fertilizer-application. Its tall alleles SD1-in and SD1-ja are harbored in indica and japonica subspecies, respectively. The sd1-d of indica IR36 was substituted with SD1-in or SD1-ja by recurrent backcrossing with IR36, and two tall isogenic lines ("5867-36" and "Koshi-36") were developed. IR36, 5867-36 and Koshi-36 were grown in a paddy field in three years, and yield and related traits were measured, the effects of SD1-in and SD1-ja on yielding ability and related characteristics were examined on the genetic background of IR 36. SD1-in decreased panicle number per m2 but increased spikelet number per panicle, ripened-grain percentage and 1000-grain weight, compared with sd1-d, resulting in the increase of yield. The increase of 1000-grain weight by SD1-in, caused by the increases of length, width and thickness of grain, was due to the increases of the length and width of lemma. SD1-ja did not significantly affect yield, mainly because the decrease of panicle number per m2 was compensated by the enlarged 1000-grain weight owing to the increase of lemma length. Serious lodging was observed in long-culmed 5867-36, suggesting that sd1-d is indispensable for indica breeding programs.

Ship motion responses and added resistance in waves have been predicted by a wide variety of computational tools. However, validation of the computational flow field still remains a challenge. In the previous study, the flow field around the Korea Research Institute for Ships and Ocean Engineering (KRISO) Very Large Crude-oil Carrier 2 tanker model with and without propeller condition and without rudder condition was measured by the authors, as well as the resistance and self-propulsion tests in waves. In this study, the KRISO container ship model appended with a rudder was used for the higher Froude number .26 and smaller block coefficient .65. The experiments were conducted in the Osaka University towing tank using a 3.2-m-long ship model for resistance and self-propulsion tests in waves. Viscous flow simulation was performed by using CFDShip-Iowa. The wave conditions proposed in Computational Fluid Dynamics (CFD) Workshop 2015 were considered, i.e., the wave-ship length ratio λ/L = .65, .85, 1.15, 1.37, 1.95, and calm water. The objective of this study was to validate CFD results by Experimental Fluid Dynamics (EFD) data for ship vertical motions, added resistance, and wake flow field. The detailed flow field for nominal wake and self-propulsion condition will be analyzed for λ/L = .65, 1.15, 1.37, and calm water. Furthermore, bilge vortex movement and boundary layer development on propeller plane, propeller thrust, and wake factor oscillation in waves will be studied.

The aim of this study was to evaluate the effects of trunk muscle mass on functional prognosis, including activities of daily living (ADLs), at hospital discharge in patients with acute stroke.This retrospective cohort study included hospitalized patients with acute stroke. Trunk muscle mass was measured using bioelectrical impedance analysis within 5 d of admission. The primary outcome was ADLs at hospital discharge, assessed using the Functional Independence Measure-motor items (FIM-motor). The secondary outcomes were hospital length of stay and discharge to home. Multivariate analyses were performed to determine the association between trunk muscle mass and FIM subitems.Data from 212 patients (mean age 72.7 y; 143 men) were included in the analysis. The median trunk muscle mass index (TMI) was 8.2 kg/msup2/supin men and 6.7 kg/msup2/supin women. Patients in the high TMI group were younger and had a higher FIM-motor score at discharge (Plt; 0.001). In multivariate analyses, TMI was positively associated with the FIM-motor score at discharge (β = 0.240, Plt; 0.001). FIM-self-care (β = 0.351, Plt; 0.001) and locomotion (β = 0.331, Plt; 0.001) were positively associated with the TMI.Trunk muscle mass is associated with ADLs at hospital discharge after acute stroke. TMI is important for evaluating functional prognosis in patients with acute stroke.

Evidence is scarce for potentially inappropriate medications (PIMs) in rehabilitation medicine.To examine the effect of PIMs on functional recovery in older patients with sarcopenia after stroke.We conducted a retrospective cohort study in a post-acute rehabilitation hospital. All patients diagnosed with sarcopenia aged ≥ 65 years among all post-stroke patients hospitalized from 2015 to 2020 were included. PIMs were defined based on the 2019 Beers criteria. Sarcopenia was diagnosed using handgrip strength (HG) and skeletal muscle mass index (SMI), according to the criteria of the Asian Working Group for Sarcopenia 2019. The outcomes included functional independence measure motor (FIM-motor), HG, and SMI values at discharge. Multiple linear regression analyses were used to determine whether PIMs used at admission were independently associated with outcomes.Of the eligible patients, 361 were 65 years or older, of whom 196 (mean age 81.0 years, 44.4% male) presented with sarcopenia and were included in the analysis. Of these, 131 (66.8%) were prescribed PIMs at admission. The most frequently prescribed PIMs were proton pump inhibitors, antipsychotics, benzodiazepines, and nonsteroidal anti-inflammatory drugs. The number of PIMs on admission was independently associated with FIM-motor (β = - 0.132, P = 0.001) and HG (β = - 0.091, P = 0.048) at discharge, but not with SMI (β = - 0.055, P = 0.256).High admission PIMs prescription numbers are negatively associated with favorable discharge functional status and muscle strength in older patients with sarcopenia after stroke.

Conventional methods for the construction of dehydroamino acids (ΔAAs), which are a unique class of non-proteinogenic amino acids, require the pre-installation of special amino acids. Herein, we report and demonstrate the practical utility of an N-chloropeptide strategy for the rapid construction of ΔAA-containing peptides. The electrophilic N-chlorination of peptide bonds is drastically accelerated by a catalytic amount of quinuclidine (ABCO), and the subsequent β-elimination of N-chloroamide efficiently provides ΔAA-containing peptides in high yield. The strategy enables, for the first time, the construction of a wide variety of ΔAA residues in peptides without any pre-functionalized side chains and facilitates the late-stage installation of ΔAA motifs into already-constructed oligopeptides, including a medicinally important macrocyclic peptide.

Background: Nontraumatic spontaneous renal hemorrhage is caused by tumor such as renal cell carcinoma or angiomyolipoma in most cases. Vasculitis including periarteritis nodosa or antineutrophil cytoplasmic antibody (ANCA)-mediated vasculitis may also be the next underlying background. Herein, we report the first case of nontraumatic spontaneous bilateral renal hemorrhage combined with chronic infection of Chlamydia pneumoniae.Case presentation: The patient serially suffered from left and right back pain within 78 days due to bilateral spontaneous renal hemorrhages. Transcatheter arterial embolization was successfully performed twice to treat serial spontaneous bilateral renal hemorrhages. The serological examination apparently revealed his chronic infection of Chlamydia pneumoniae and a slight elevation of anti-deoxy nucleotide antibodies. Furthermore, computed tomography (CT) angiogram and 67galium citrate scintigram also suggested underlining severe arteriosclerosis without severe inflammation in bilateral kidneys. Chronic infection of Chlamydia pneumoniae and underlying autoimmune vasculitis may pull a trigger of bilateral spontaneous renal hemorrhages although the real mechanisms remain unknown. Conclusions: In conclusion, we reported an extremely rare case of nontraumatic spontaneous bilateral renal hemorrhage of unknown etiology. Severe atherosclerosis caused by chronic infection due to Chlamydia pneumoniae may predispose to the vascular vulnerability of the bilateral renal arteries in close association with hypertension, oral intake of antiplatelets, and underlying autoimmune vasculitis.

Pharmacotherapy is important in older patients undergoing rehabilitation because such patients, especially those with frailty and physical disabilities, are susceptible to drug-related functional impairment. Drug-related problems include polypharmacy, potentially inappropriate medications (PIMs), and potential prescription omissions. These problems are associated with adverse drug events such as dysphagia, depression, drowsiness, falls and fractures, incontinence, decreased appetite, and Parkinson's syndrome, leading to impaired improvement in activities of daily living (ADL), quality of life (QOL), and nutritional status. Moreover, the anticholinergic burden is associated with impaired physical and cognitive functions. Therefore, pharmacist-centered multidisciplinary pharmacotherapy should be performed to maximize rehabilitation outcomes. Pharmacotherapy includes a review of all medications, the assessment of drug-related problems, goal setting, correction of polypharmacy and PIMs, monitoring of drug prescriptions, and reassessment of drug-related problems. The goal of pharmacotherapy in rehabilitation medicine is to optimize drug prescribing and to maximize the improvement of ADL and QOL as patient outcomes. The role of pharmacists during rehabilitation is to treat patients as part of multidisciplinary teams and as key members of nutritional support teams. In this review, we aim to highlight existing evidence regarding pharmacotherapy in older adults, including drug-related functional impairment and the association between pharmacotherapy and functional, cognitive, and nutritional outcomes among patients undergoing rehabilitation. In addition, we highlight the important role of pharmacists in maximizing improvements in rehabilitation outcomes and minimizing drug-related adverse effects.

Background: The use of antipsychotics have been shown to affect activities of daily living during rehabilitation, but reports regarding their effects on older patients with sarcopenia are insufficient. Aim: To establish whether the use of antipsychotics has effects on muscle strength and muscle mass in older patients with sarcopenia undergoing convalescent rehabilitation after stroke.Methods: This retrospective cohort study was conducted at a rehabilitation hospital between 2015 and 2020. The study outcomes included skeletal muscle mass index and hand grip strength at discharge. Multivariate analyses were used to determine whether the use of antipsychotics at admission and at 4 weeks after admission were independently associated with the study outcomes, after adjusting for potential confounders.Results: Of the 619 stroke patients admitted, 196 (mean age 81 years; 44.4% men) had sarcopenia at admission and were included in the final analysis. The median hand grip strength and median skeletal muscle mass index values were 12.5 (5.9–17.9) kg and 5.1 (4.5–6.0) kg/m2, respectively. In the multivariate analyses, the use of antipsychotics at 4 weeks post-admission was independently associated with hand grip strength at discharge (β = –0.125, p = 0.008), which was not the case when used at admission. Furthermore, the use of antipsychotics at admission and at 4 weeks after admission were not significantly associated with the skeletal muscle mass index at discharge.Conclusions: The use of antipsychotics in older patients with sarcopenia after stroke was negatively associated with handgrip strength at discharge.

BackgroundEvidence is scarce regarding the polypharmacy and potentially inappropriate medications (PIMs) in rehabilitation medicine.AimTo investigate the prevalence and impact on outcomes of polypharmacy and PIMs in stroke rehabilitation.MethodsA retrospective cohort study was conducted with 849 older inpatients after stroke.Polypharmacy was defined as six or more medications, and PIMs were defined based on Beers criteria 2019. Study outcomes included Functional Independence Measure (FIM)-motor, FIM-cognitive, energy intake, dysphagia, length of hospital stay and the rate of home discharge. To consider the impact of pharmacotherapy during rehabilitation, multivariate analyses were used to determine whether the presence of polypharmacy or PIMs at discharge was associated with outcomes.ResultsAfter enrollment, 361 patients (mean age 78.3 ± 7.7 years; 49.3% male) were analyzed. Polypharmacy was observed in 43.8% and 62.9% of patients, and any PIMs were observed 64.8% and 65.4% of patients at admission and discharge, respectively. The most frequently prescribed PIMs included antipsychotics, benzodiazepines, and proton pump inhibitors. Polypharmacy was negatively associated with FIM-motor score (β = -0.072, P = 0.017), FIM-cognitive score (β = -0.077, P = 0.011), energy intake (β = -0.147, P = 0.004), and home discharge (OR: 0.499; 95% CI: 0.280, 0.802; P = 0.015). PIMs were negatively associated with energy intake (β = -0.066, P = 0.042) and home discharge (OR: 0.452; 95% CI: 0.215, 0.756; P = 0.005).ConclusionsPolypharmacy and PIMs are commonly found among older patients undergoing stroke rehabilitation. Moreover, polypharmacy and PIMs are negatively associated with outcomes.

Energy intake and rehabilitation time individually contribute to the improvement of activities of daily living (ADL). This study aimed to investigate the additive effect of energy intake and rehabilitation time on ADL improvement in acute stroke patients with sarcopenia. The study included 140 patients (mean age 82.6 years, 67 men) with stroke. Energy intake during the first week of hospitalization was classified as “Sufficiency” or “Shortage” based on the reported cutoff value and rehabilitation time was classified as “Long” or “Short” based on the median. The study participants were categorized into four groups based on the combination of energy intake and rehabilitation time. The primary outcome was the gain of functional independence measure (FIM) motor during hospitalization. The secondary outcomes were length of stay and home discharge rates. Multivariate analysis was performed with primary/secondary outcomes as the dependent variable, and the effect of each group on the outcome was examined. Multivariate analysis showed that “long rehabilitation time and sufficient energy intake” (β = 0.391, p < 0.001) was independently associated with the gain of FIM motor items. The combination of high energy intake and sufficient rehabilitation time was associated with ADL improvement in acute stroke patients with sarcopenia.

Background Evidence is scarce regarding polypharmacy and potentially inappropriate medications (PIMs) in rehabilitation medicine. Aim To investigate the prevalence of polypharmacy and PIMs and their association with outcomes in stroke rehabilitation. Method A retrospective cohort study was conducted with 849 older inpatients post-stroke. Polypharmacy was defined as six or more medications, and PIMs were defined based on Beers criteria 2019. Study outcomes included functional independence measure (FIM)-motor, FIM-cognitive, energy intake, dysphagia, length of hospital stay, and the rate of home discharge. To consider the effect of pharmacotherapy during rehabilitation, multivariate analyses were used to determine whether the presence of polypharmacy or PIMs at discharge was associated with outcomes. Results After enrollment, 361 patients (mean age 78.3 ± 7.7 years; 49.3% male) were analyzed. Polypharmacy was observed in 43.8% and 62.9% of patients, and any PIMs were observed in 64.8% and 65.4% of patients at admission and discharge, respectively. The most frequently prescribed PIMs included antipsychotics, benzodiazepines, and proton pump inhibitors. Polypharmacy was negatively associated with FIM-motor score (β = - 0.062, P = 0.049), FIM-cognitive score (β = - 0.076, P = 0.014), energy intake (β = - 0.143, P = 0.005), and home discharge (OR: 0.458; 95% CI: 0.248, 0.847; P = 0.013). PIMs were negatively associated with home discharge (OR: 0.375; 95% CI: 0.195, 0.718; P = 0.003). Conclusion Polypharmacy and PIMs are commonly found among older patients undergoing stroke rehabilitation. Moreover, polypharmacy was negatively associated with activities of daily living (ADL) but not with PIMs and ADLs, and both were associated with home discharge.

Sarcopenic obesity is of growing research and clinical interest; however, validated diagnostic criteria are lacking. We therefore aimed to examine the prevalence of sarcopenic obesity as diagnosed by the criteria recently proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO), and its association with outcomes among patients after stroke. This study was based on a cohort of 760 Japanese patients after stroke admitted to a post-acute rehabilitation hospital. Sarcopenic obesity was diagnosed at admission according to the ESPEN and EASO criteria using reference values specific to Asians. Outcomes included the motor domain of the functional independence measure (FIM-motor) and the food intake level scale (FILS) at discharge. Multivariate linear regression models were used to assess the associations between sarcopenic obesity and outcomes. Among 760 patients (median age, 73 years; 352 women and 408 men), sarcopenic obesity was diagnosed in 34 patients (4.5%; 5.4% of women and 4.1% of men). In multivariate analyses, sarcopenic obesity was independently and negatively associated with FIM-motor (β = −0.048, p = 0.031) and FILS at discharge (β = −0.095, p = 0.046) in women. In contrast, in men, sarcopenic obesity showed an independent negative association with FIM-motor at discharge (β = −0.117, p < 0.001) but no statistically significant association with FILS at discharge (β = −0.004, p = 0.323). In conclusion, the prevalence of sarcopenic obesity diagnosed by the ESPEN and EASO-defined criteria was as low as 4.5% among Japanese patients after stroke. Furthermore, sarcopenic obesity was negatively associated with improvements in activities of daily living and dysphagia.

Evidence regarding the effect of sarcopenic obesity on recovery in stroke patients is scarce in rehabilitation medicine. The aim of this study was to examine the association between changes in muscle strength and functional outcomes in patients with sarcopenic obesity undergoing rehabilitation after stroke.This study was a retrospective cohort study of stroke patients, consecutively admitted to post-acute rehabilitation wards of a single hospital, of which, only those diagnosed with sarcopenic obesity at admission were included in the final analysis. Bioimpedance analysis was used to measure skeletal muscle mass and body fat mass. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Sarcopenia was diagnosed using muscle mass index and handgrip strength. Obesity was diagnosed using body fat percentage (men ≥30%, women ≥35%). The evaluated outcomes were Functional Independence Measure (FIM)-motor score at discharge and its gain. Multiple regression analysis was used to verify whether changes in hand grip strength during hospitalization were associated with functional outcomes.Sixty-two patients (29 men) with a mean age of 78 years, were analyzed. The mean change in the hand grip strength was 3.9 kg. In multiple regression analysis, changes in the hand grip strength were significantly associated with FIM-motor at discharge (β = 0.34, P0.01) and FIM-motor gain (β = 0.58, P0.01).Muscle strength gain was associated with improved functional recovery in stroke patients with sarcopenic obesity.

A photo-responsive nanoscroll composed of niobate nanosheets and a polyfluoroalkyl azobenzene derivative (C3F-Azo-C6H) is one of the most interesting layered materials because the reversible winding and unwinding motion could be efficiently induced by photo-irradiations. Previously, we have studied a double-walled nanoscroll (DWNS) of niobate that could be synthesized by the intercalation of a cationic polyfluorinated surfactant only into the interlayer I of the layered niobate among the two interlayers, I and II. In this study, we have successfully synthesized another novel photo-responsive single-walled nanoscroll (SWNS) of niobate by a stepwise guest–guest ion-exchange method. All niobate nanosheets that were exfoliated at both interlayers I and II were efficiently converted to nanoscrolls by the intercalation of C3F-Azo-C6H. The synthetic yield has been quantitatively estimated. Though the photo-isomerization reaction of C3F-Azo-C6H was induced in the SWNS, its photo-reactivity was the lowest when compared with those of the nanosheet-stacked film and the DWNS. The photo-reactivity of C3F-Azo-C6H decreased in the order of DWNS > nanosheet-stacked film > SWNS. The different flexibility of the layered miroenvironment might influence the photo-reactivity of C3F-Azo-C6H in the niobate hybrid. The SWNS exhibited a reversible expansion and shrinkage of its interlayer spaces upon photo-irradiation, while the winding and unwinding motion was not observed, contrary to the DWNS. The direction of the expansion and shrinkage of the interlayer of the SWNS was opposite to those of the nanosheet-stacked film and the DWNS. Based on the experimental results, the tilt angle of C3F-Azo-C6H against the nanosheet surface and the matching structures of the top and bottom surfaces of the nanosheet could be the probable key factors that control the photo-reactivity of C3F-Azo-C6H in the layered microenvironment; the morphological changes of the nano hybrids was also discussed.

Evidence is scarce regarding the polypharmacy in patients with sarcopenia. The aim of this study was to investigate the effect of deprescribing for polypharmacy on the improvement of nutritional intake and sarcopenia in older patients with sarcopenia. A retrospective cohort study was conducted with hospitalized older patients with sarcopenia undergoing rehabilitation after stroke. Study outcomes included energy intake, protein intake, handgrip strength (HG) and skeletal muscle mass index (SMI) at hospital discharge. To consider the effects of deprescribing for polypharmacy, we used multivariate analyses to examine whether the change in the number of medications during hospitalization was associated with outcomes. Of 361 patients after enrollment, 91 (mean age 81.0 years, 48.4% male) presented with sarcopenia and polypharmacy and were eligible for analysis. The change in the number of medications was independently associated with energy intake (β = −0.237, p = 0.009) and protein intake (β = −0.242, p = 0.047) at discharge, and was not statistically significantly associated with HG (β = −0.018, p = 0.768) and SMI (β = 0.083, p = 0.265) at discharge, respectively. Deprescribing was associated with improved nutritional intake in older sarcopenic patients with polypharmacy undergoing stroke rehabilitation.

Despite CYP102A1 (P450BM3) representing one of the most extensively researched metalloenzymes, crystallisation of its haem domain upon modification can be a challenge. Crystal structures are indispensable for the efficient structure-based design of P450BM3 as a biocatalyst. The abietane diterpenoid derivative N-abietoyl-l-tryptophan (AbiATrp) is an outstanding crystallisation accelerator for the wild-type P450BM3 haem domain, with visible crystals forming within 2 hours and diffracting to a near-atomic resolution of 1.22 A. Using these crystals as seeds in a cross-microseeding approach, an assortment of P450BM3 haem domain crystal structures, containing previously uncrystallisable decoy molecules and diverse artificial metalloporphyrins binding various ligand molecules, as well as heavily tagged haem-domain variants, could be determined. Some of the structures reported herein could be used as models of different stages of the P450BM3 catalytic cycle.

A skewed TCR repertoire does not directly trigger inflammation in adipose tissue, Obesity is accompanied by chronic, low-grade inflammation in adipose tissue, which is associated with insulin resistance and consequent multiple metabolic diseases. In addition to M1 macrophage infiltration, multiple involvements of adipose tissue T lymphocytes in the progression of inflammation have been highlighted recently. Here, we isolated a specific Vα5/Vβ8.2 TCR-bearing T cell that accumulated in obese adipose tissue of mice, and generated transgenic mice expressing this TCR. Under lean conditions with a normal chow diet, CD4+FoxP3+ Treg cells and M2 macrophages increased in adipose tissue with ageing in wild-type mice, but not in transgenic mice. However, both mice exhibited no obvious adipose tissue inflammation such as the formation of crown-like structures (CLSs) of infiltrating macrophages. When fed a high-fat diet, the proportion of adipose tissue Treg cells was markedly small at a similar level in transgenic and wild-type mice. Both types of mice exhibited comparable inflammatory states in adipose tissue, including vast formation of macrophage CLSs, accompanied by insulin resistance. Together, our findings suggest that the absence of an increase in Treg cells and M2 macrophages is not sufficient to initiate inflammatory macrophage infiltration in lean adipose tissue and also provide a new view about the involvement of T cells in promoting obesity-associated inflammation.

A supervised machine learning algorithm, which is qualified for image classification and analyzing similarities, is based on multiple discriminative morphological features that are automatically assembled during the learning processes. The algorithm is suitable for population-based analysis of images of biological materials that are generally complex and heterogeneous. Here we used the algorithm wndchrm to quantify the effects on nucleolar morphology of the loss of the components of nuclear envelope in a human mammary epithelial cell line. The linker of nucleoskeleton and cytoskeleton (LINC) complex, an assembly of nuclear envelope proteins comprising mainly members of the SUN and nesprin families, connects the nuclear lamina and cytoskeletal filaments. The components of the LINC complex are markedly deficient in breast cancer tissues. We found that a reduction in the levels of SUN1, SUN2, and lamin A/C led to significant changes in morphologies that were computationally classified using wndchrm with approximately 100% accuracy. In particular, depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis. Further, wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. Our unbiased morphological quantitation strategies using wndchrm revealed an unexpected link between the components of the LINC complex and the morphologies of nucleoli that serves as an indicator of the malignant phenotype of breast cancer cells.

In suitable environments, weathering steels can be used for bridges without anticorrosion painting, because weathering steels have enough resistance to atmospheric corrosion by the protective rust generated on its surface. While, abundant supply of salt causes serious corrosion damage on weathering steels. Hence, deterioration due to corrosion is found in weathering steel bridges in conditions that salt abundantly supplied. When serious damages with corrosion are found in the components of weathering steel bridges, salt abundance on the components is measured to estimate reason of the corrosion and determine the repairing method. The salt abundance on the components is usually measured by surface salinity checker, which determines salt abundance by electrical conductivity of water that is in contact with an analyzed area. However, measurement of salt abundance by surface salinity checker is difficult for the component with serious corrosion damages, because porous rust or rough surface on the damaged component cause leakage of the contact water during the analysis. Therefore, measuring method for salt abundance without using water is needed to know salt abundance on corroded components for the maintenance of weathering steel bridges. In order to discuss the possibility of salt abundance measurement by portable XRF, characteristic X-ray intensity of Cl-and abundance of Cl- on five types of test pieces of weathering steels were analyzed by portable x-ray fluorescence analyzer (XRF) and gauze wipe method with ion chromatography respectively, in this study. The two types of test pieces are new weathering steels with coating of A-5 or C-5. Three types of test pieces were artificially corroded previously. For the two types of the corroded test pieces, coating with Ra-III or Rc-I were applied after removing rust. The other type of corroded test pieces was used without rust removing and coatings. The rust thickness on the test pieces was about a few 100 µm. To make air-born salt accumulation on each test pieces, sheltered exposure test was performed in the test site on the roof of the three-story building of the National institute of Technology, Matsue College, which is about 10 km far from sea. After that, characteristic X-ray intensity of Cl- on the test pieces was measured by portable XRF. Cl- on the test pieces was sampled by gauze wiping method, and the Cl- abundance was analyzed by ion chromatography. The characteristic X-ray intensity and abundance of Cl- on test pieces with coatings show good correlation (Fig. 1), suggesting that portable XRF is possible tool for measurement of Cl- abundance on the steels. While, the intensity of characteristic X-ray of Cl- on the corroded test pieces without removing rust shows poor correlation with the Cl- abundance. The intensity of characteristic X-ray of Cl- on the corroded test pieces without removing rust is extremely higher than that estimated from its Cl- abundance by gauze wiping method, considering the correlation among the test pieces with coatings. Since Cl- on weathering steels are known to be also in rust [3], completely sampling of Cl- by gauze wipe method is probably difficult for the corroded test pieces. Considering to the correlation line among the test pieces with coatings, the X-ray intensity of Cl- on corroded test pieces without removing rust potentially suggests that Cl- abundance on the test pieces are a few 100 mg/m2. For more accurate measurement of Cl- abundance on weathering steels with rust, the clear relation between characteristic X-ray intensity and Cl- abundance on weathering steels covered with rust should be revealed. To found the relation, method for complete sampling of Cl- on weathering steels with rust is required. In addition, it is needed to investigate detection range of Cl- in rust of weathering steels by portable XRF in terms of depth direction from surface. References [1] T. Kamimura, S. Hara, H. Miyuki, M. Yamashita, H. Uchida, Composition and protective ability of rust layer formed on weathering steel exposed to various environments, Corros. Sci. 48 (2006) 2799–2812. [2] S. Hara, T. Kamimura, H. Miyuki, M. Yamashita, Taxonomy for protective ability of rust layer using its composition formed on weathering steel bridge, Corros. Sci. 49 (2007) 1131–1142. [3] A.Imai, M. Gagasawa, K. Ishida, M. Sano, H.Kihira, Study on surface state monitoring methods with supplemental rust controlling surface treatment, Journal of Japan Society of Civil Engineers, 70 (2014) 252-264. Acknowledgement We wish to express appreciation to Dr. Imai, Nippon Steel, Anti-Corrosion Co., Ltd. for supporting the analysis by portable XRF. Figure 1

Background/aim Chemotherapy is an important first-line treatment for oesophageal squamous cell carcinoma (ESCC). However, there are few secondary options. Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, enhances the cytotoxicity of various anticancer drugs and has been used to treat advanced ovarian and breast cancers. This study examined the effect of olaparib on the cytotoxicity of anticancer drugs in ESCC cell lines. Materials and methods ESCC KYSE70 and KYSE140 cells were grown in Dulbecco's modified Eagle's medium and treated with 5-fluorouracil (5-FU), cisplatin, docetaxel, doxorubicin, SN-38, or temozolomide without or with olaparib. Results Olaparib enhanced the cytotoxicity of all tested anticancer drugs and increased the effects of cisplatin, doxorubicin, SN-38, and temozolomide synergistically. These anticancer drugs caused the accumulation of phospho-histone H2AX Ser139 (γH2AX), a biomarker of DNA damage, and olaparib increased this accumulation. Conclusion PARP inhibitors may potentiate the anticancer activity of DNA-damaging agents in ESCC patients synergistically.

The linker of nucleoskeleton and cytoskeleton (LINC) complex, containing the proteins SUN and nesprin, is the fundamental structural unit of the nuclear envelope. The neoplastic-based regulation of the LINC complex in cancer tissues has become increasingly recognized in recent years, including the altered expression, somatic mutation, and methylation of genes. However, precisely how mutations and deregulated expression of the LINC complex contribute to the pathogenic mechanisms of tumorigenesis remain to be elucidated, mainly because of several technical difficulties. First, both the SUN and SYNE (encoding nesprin) genes give rise to a vast number of splicing variants. Second, immunoprecipitation experiments of endogenous SUN and nesprin proteins are difficult owing to the lack of suitable reagents as well as the limited solubility of these proteins in mild extraction conditions. Here, we describe three protocols to investigate these aspects: (1) immunohistochemistry to determine the expression levels and localization of the LINC complex in cancer tissue, (2) detection of SUN1 splicing variants at the mRNA level, and (3) detection of SUN1 splicing variants and binding partners at the protein level.

Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.

Cancer cells exhibit a variety of features indicative of atypical nuclei. However, the molecular mechanisms underlying these phenomena remain to be elucidated. The linker of nucleoskeleton and cytoskeleton (LINC) complex, a nuclear envelope protein complex consisting mainly of the SUN and nesprin proteins, connects nuclear lamina and cytoskeletal filaments and helps to regulate the size and shape of the nucleus. Using immunohistology, we found that a nuclear lamina component, lamin A/C and all of the investigated LINC complex components, SUN1, SUN2, and nesprin-2, were downregulated in human breast cancer tissues. In the majority of cases, we observed lower expression levels of these analytes in samples' cancerous regions as compared to their cancer-associated noncancerous regions (in cancerous regions, percentage of tissue samples exhibiting low protein expression: lamin A/C, 85% [n = 73]; SUN1, 88% [n = 43]; SUN2, 74% [n = 43]; and nesprin-2, 79% [n = 53]). Statistical analysis showed that the frequencies of recurrence and HER2 expression were negatively correlated with lamin A/C expression (P

The linker of nucleoskeleton and cytoskeleton (LINC) complex, containing the proteins SUN and nesprin, is the fundamental structural unit of the nuclear envelope. The neoplastic-based regulation of the LINC complex in cancer tissues has become increasingly recognized in recent years, including the altered expression, somatic mutation, and methylation of genes. However, precisely how mutations and deregulated expression of the LINC complex contribute to the pathogenic mechanisms of tumorigenesis remain to be elucidated, mainly because of several technical difficulties. First, both the SUN and SYNE (encoding nesprin) genes give rise to a vast number of splicing variants. Second, immunoprecipitation experiments of endogenous SUN and nesprin proteins are difficult owing to the lack of suitable reagents as well as the limited solubility of these proteins in mild extraction conditions. Here, we describe three protocols to investigate these aspects: (1) immunohistochemistry to determine the expression levels and localization of the LINC complex in cancer tissue, (2) detection of SUN1 splicing variants at the mRNA level, and (3) detection of SUN1 splicing variants and binding partners at the protein level.

Two new cytotoxic dilactones, bisisorhizopodin (1) and isorhizopodin (2), together with known divalent actin depolymerizer rhizopodin (3), were isolated from the culture broth of a myxobacterium Myxococcus stipitatus. Spectroscopic analyses established that 1 and 2 are doubly and singly acyl-migrated isomers of 3, respectively, and comparison of their cytotoxicity revealed gradual decrease in the activity as the size of the ring contracted. Because the side chains of macrolide toxins uniformly block the contact between the actin protomers, the present result demonstrates substantial contribution of structurally diverse rings to the affinity of macrolide toxins for its target protein.

Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation. Here we found a physiological AIM-cleavage process that induces destabilization of AIM and its excretion in urine. In blood, IgM-free AIM appeared to be cleaved and reduced in size approximately 10 kDa. Cleaved AIM was unable to bind to IgM and was selectively filtered by the glomerulus, thereby excreted in urine. Amino acid substitution at the cleavage site resulted in no renal excretion of AIM. Interestingly, cleaved AIM retained a comparable potency with full-length AIM in facilitating the clearance of dead cell debris in injured kidney, which is a key response in the recovery of acute kidney injury. Identification of AIM-cleavage and resulting functional modification could be the basis for designing safe and efficient AIM therapy for various diseases.

Chromosome elimination occurs frequently in interspecific hybrids between distantly related species in Poaceae. However, chromosomes from both parents behave stably in a hybrid of female oat (Avena sativa L.) pollinated by pearl millet (Pennisetum glaucum L.). To analyze the chromosome behavior in this hybrid, we cloned the centromere-specific histone H3 (CENH3) genes of oat and pearl millet and produced a pearl millet-specific anti-CENH3 antibody. Application of this antibody together with a grass species common anti-CENH3 antibody revealed the dynamic CENH3 composition of the hybrid cells before and after fertilization. Despite co-expression of CENH3 genes encoded by oat and pearl millet, only an oat-type CENH3 was incorporated into the centromeres of both species in the hybrid embryo. Oat CENH3 enables a functional centromere in pearl millet chromosomes in an oat genetic background. Comparison of CENH3 genes among Poaceae species that show chromosome elimination in interspecific hybrids revealed that the loop 1 regions of oat and pearl millet CENH3 exhibit exceptionally high similarity.

Acetaminophen analogues containing α-amino acid and fatty acids were easily synthesized in 77–99% yields from the corresponding mixed carbonic carboxylic anhydrides of α-amino acid and fatty acids using aniline derivatives in aqueous MeCN.

Exocrine gland-secreting peptide 1 (ESP1) released into male tear fluids is a male pheromone that stimulates sexually receptive behavior in female mice via the vomeronasal sensory system. ESP1 also induces c-Fos expression in male brain regions distinct from those in females. However, behavior in males following ESP1 exposure has not been examined. In the present study, we show that ESP1, in conjunction with unfamiliar male urine, enhances male aggression via the specific vomeronasal receptor V2Rp5. In addition, male mice that secrete ESP1 but lack V2Rp5 exhibit a lower level of aggressiveness than do mice that express V2Rp5. These results suggest that ESP1 not only acts as a male pheromone in both sexes but also serves as an auto-stimulatory factor that enhances male aggressiveness by self-exposure. Finally, re-activation of ESP1-induced c-Fos-positive neurons by using the designer receptor exclusively activated by designer drug (DREADD) approach resulted in enhancement of sexual and aggressive behaviors in female and male mice, respectively, indicating that sexually dimorphic activation in the brain is a neural basis for the sex-specific behavioral responses to ESP1.