Interspecific social dominance networks reveal mechanisms promoting coexistence in sympatric charr in Hokkaido, Japan.

Coexistence of species requires equalizing mechanisms that minimize fitness differences, which are balanced by stabilizing mechanisms that enhance negative intraspecific interactions versus interspecific ones. Here, we develop a simple theoretical framework that allows measuring the relative strength of intraspecific versus interspecific competition in dominance hierarchies. We use it to evaluate mechanisms promoting coexistence between two congeneric charr that compete for foraging positions, which strongly influence density-dependent growth and survival. Agonistic interactions (n = 761) among 71 Dolly Varden Salvelinus malma and whitespotted charr Salvelinus leucomaenis were measured by snorkelling in two pools in the sympatric zone of a Hokkaido stream during two summers. Interspecific dominance hierarchies, analysed using three methods, were closely correlated with fish length but the species treated each other equally. Ranks for the most dominant fish in each pool, determined directly by knockout experiments, were also virtually identical to ranks by length. Similarly, exponential random graph modelling of the social networks provided no evidence that either species was dominant over the other. Instead, larger fish were more likely to win contests, especially over fish of the next lower ranks. These results demonstrated that the two species were nearly ecological equivalents in accessing key resources in this sympatric zone. Nearly identical growth and stable densities over 4 years further supported this inference, although Dolly Varden were a minority (29% of the assemblage), a sign of some fitness difference. Detailed foraging observations coupled with two concurrent studies revealed an effective stabilizing mechanism. Dolly Varden shifted to feeding directly from the benthos when drifting invertebrates declined, a behaviour enhanced by morphological character displacement, thereby partitioning food resources and enhancing intraspecific competition while avoiding agonistic encounters with whitespotted charr. The plurality of evidence indicates that fitness differences between these ecologically equivalent species are small in this local assemblage, and balanced by resource partitioning, a modest stabilizing mechanism that promotes coexistence. The theoretical framework presented here is a useful tool to evaluate the strength of interspecific versus intraspecific competition, which combined with information on trade-offs in ecological performance can contribute to a mechanistic understanding of species coexistence.

[Thrombectomy for right atrial thrombosis complicating a pyogenic liver abscess].

Vascular complications from a liver abscess are rare but life-threatening. Herein, we report the case of a man in his 40s with a pyogenic hepatic abscess complicated by an inferior vena caval thrombus extending to the right atrium. His presenting complaint was a high fever. Blood tests revealed elevated inflammatory markers and liver enzymes. An abdominal CT demonstrated a 10cm abscess in the right hepatic lobe. A blood culture grew Streptococcus intermedius, which was sensitive to ampicillin sulbactam. He was diagnosed with a pyogenic liver abscess and treated with metronidazole and ampicillin sulbactam. Three days following admission, an abdominal CT scan revealed the thrombus extending from the liver abscess into the right atrium. He underwent thrombectomy and received antibiotic therapy. Postoperatively, abdominal ultrasound revealed a significant decrease in the size of the hepatic abscess. The patient was discharged in good condition on the 46th day of hospitalization. When encountering a hepatic abscess, it is important to consider that it may be associated with a thrombus extending from the inferior vena cava into right atrium.

Prevalence of primary aldosteronism without hypertension in the general population: Results in Shika study.

OBJECTIVE: Recent studies have reported a high prevalence of primary aldosteronism (PA) among hypertensive patients. However, few data exist regarding the prevalence of PA in the general population. Therefore, we examined the prevalence of PA in the general population including normotensive subjects. METHODS: Plasma renin activity (ng/mL/hr), plasma aldosterone concentration (pg/mL) and aldosterone renin ratio (ARR) were determined in 309 subjects aged >40 years in Horimatsu and Higashi-Matsuho district, Shika-machi, Ishikawa, Japan. RESULTS: Among them, 195 subjects (78 males, mean age: 62 ± 11 years) did not take antihypertensive agents: 113 normotensive subjects and 82 hypertensive subjects. Under these conditions, 68 subjects (13 males, age 62 ± 10 years) had an ARR >200. In 14 subjects who underwent captopril suppression test, PA was documented in 5 subjects, yielding a minimum prevalence of 2.6% in total subjects (1.8% in normotensive subjects and 3.7% in hypertensive subjects). Interestingly, females subjects demonstrated significant differences in ARR between subjects with age <50 (172 ± 105) and those with age 51-60 (388 ± 531), although there were no differences in male subjects. CONCLUSIONS: These results demonstrate that PA including normotensive subjects exists more commonly than that expected in the general population. We suggest further investigation about the cause and progression of PA associated with sex and aging.

Specific detection by the polymerase chain reaction of potentially allergenic salmonid fish residues in processed foods.

Salmonid fish is one of the allergenic items that are recommended to be labeled in the Japanese allergen-labeling system. This study develops a salmonid-specific polymerase chain reaction (PCR) method. A new primer pair, SKE-F/SKE-R, was designed to specifically detect the salmonid fish gene encoding mitochondrial DNA cytochrome b. Genomic DNAs extracted from 58 kinds of seafood and 11 kinds of processed food were individually subjected to PCR by using the primer pair, and a salmonid-specific fragment of 212 bp was only amplified in the salmonid samples and salmonid-containing processed foods. The detection limit of the PCR method was as low as 0.02 fg/µL of salmonid fish DNA (corresponding to 10 copies). There is no ELISA method for salmonid fish, making our PCR method the only reliable measure for detecting salmonid fish in processed foods.

Clinical evaluation of hemorrhagic gastroduodenal ulcer in the elderly: is Helicobacter pylori infection a risk factor for hemorrhage?

AIM: In this study, the aim was to determine the demographic characteristics of elderly patients with gastroduodenal ulcer who had undergone endoscopic hemostasis by comparing them with younger patients. METHODS: A total of 353 patients with Forrest class I-IIa hemorrhagic gastroduodenal ulcer who underwent endoscopic hemostasis at our hospital between December 2004 and May 2010 were divided into two groups: one for those 75 years or older (old-old group; n = 71; age ≥75 years) and one for those younger than 75 years (younger group; n = 282; age <75 years). Then, their demographic characteristics were compared. RESULTS: There were significantly more female patients, patients with underlying chronic renal failure and patients using non-steroidal anti-inflammatory drugs in the old-old group than in the younger group. In addition, the prevalence of open-type atrophy in the background gastric mucosa was significantly higher in the old-old group. Although more than half the patients in each group were infected with Helicobacter pylori, the prevalence was significantly higher in the younger group. Of the patients who underwent endoscopic hemostasis only once, those in the old-old group constituted a significantly higher medical cost than those in the younger group. Comparison of deaths between the two groups revealed that the old-old patients were more likely to develop severe complications associated with hematemesis, such as aspiration pneumonia. CONCLUSIONS: The observed lower prevalence of Helicobacter pylori infection among the elderly patients compared to the younger patients with hemorrhagic gastroduodenal ulcer suggests that other factors, such as non-steroidal anti-inflammatory drugs use and chronic renal failure, predispose the elderly to hemorrhagic ulcer.

Measurement of skeletal muscle volume is useful for predicting prognosis in patients with liver cirrhosis.

BACKGROUND: Hepatic venous pressure gradient (HVPG) and the model for end-stage liver disease (MELD) score were previously reported as prognostic factors for outcome in patients with liver cirrhosis (LC), and recently, the presence of sarcopenia was reported to be an indicator of worse prognosis in these patients. AIM: This retrospective study aimed to clarify the importance of sarcopenia as a prognostic factor in patients with LC. MATERIAL AND METHODS: The MELD-Na score, HVPG, and skeletal muscle index (SMI) were measured in 202 patients between January 2013 and August 2020. We performed linear regression analysis between HVPG and SMI and calculated suitable cutoff values of HVPG for predicting presarcopenia and of HVPG, ΔSMI (i.e. the decrease in SMI per year, for predicting survival). Overall survival rates with the HVPG and ΔSMI cutoff values were compared by Kaplan-Meier estimates and log-rank tests. Prognostic factors for survival were analyzed by Cox regression univariate and multivariate analyses. RESULTS: In total, 71% (143/202) of patients presented with presarcopenia. Linear regression showed a significantly negative correlation between HVPG and SMI. Survival was significantly worse in the group with presarcopenia than in the group without. Survival was worse also in the group with an HVPG value ≥ 15 and ΔSMI ≥ -2.4. Cox regression multivariate analyses showed that MELD-Na score, HVPG, HVPG ≥ 15, ΔSMI, and ΔSMI ≥ -2.4 were independent prognostic factors. CONCLUSION: Skeletal muscle volume, especially ΔSMI, has a prognostic value equivalent to that of the MELD-Na score and HVPG.

Distribution and genome structures of temperate phages in acetic acid bacteria.

Acetic acid bacteria (AAB) are industrial microorganisms used for vinegar fermentation. Herein, we investigated the distribution and genome structures of mitomycin C-inducible temperate phages in AAB. Transmission electron microscopy analysis revealed phage-like particles in 15 out of a total 177 acetic acid bacterial strains, all of which showed morphology similar to myoviridae-type phage. The complete genome sequences of the six phages derived from three strains each of Acetobacter and Komagataeibacter strains were determined, harboring a genome size ranging from 34,100 to 53,798 bp. A phage AP1 from A. pasteurianus NBRC 109446 was predicted as an active phage based on the genomic information, and actually had the ability to infect its phiAP1-cured strain. The attachment sites for phiAP1 were located in the 3'-end region of the tRNAser gene. We also developed a chromosome-integrative vector, p2096int, based on the integrase function of phiAP1, and it was successfully integrated into the attachment site of the phiAP1-cured strain, which may be used as a valuable tool for the genetic engineering. Overall, this study showed the distribution of mitomycin C-inducible temperate phages in AAB, and identified the active temperate phage o f A. pasteurianus.

Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: In clinical practice, whether cirrhotic livers in patients with hepatocellular carcinoma (HCC) can withstand repeated stereotactic body radiation therapy (SBRT) remains unclear. This study aimed to evaluate the outcomes and toxicities in these patients. METHODS AND MATERIALS: This retrospective study included patients with HCC who were treated with SBRT at least twice between January 2012 and June 2019. Local control and overall survival rates were calculated. Liver function before and after irradiation was evaluated using the Child-Pugh score and modified albumin-bilirubin grade. All toxicities were assessed using the Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Fifty-two patients underwent 136 courses (148 lesions) of SBRT, which was mostly performed for out-of-field tumors but 3 in-field recurrences. The median follow-up duration from the first SBRT was 52.6 months (range, 15.7-89.3 months). The median gross tumor volume was 4.6 cm3 (range, 0.8-55.2 cm3) at the second SBRT. The 3-year local control rate was 94.5% (95% confidence interval, 88.0%-97.5%). The 3-year overall survival rate after the second course was 62.8% (95% confidence interval, 45.1%-76.2%). Although the Child-Pugh score did not deteriorate after the second course, deterioration of the modified albumin-bilirubin grade at 6, 12, and 24 months was statistically significant compared with that before the second course. One patient (1.9%) experienced grade 3 hypoalbuminemia and 2 patients (3.8%) had grade 3 thrombocytopenia 6 months after the second course. Mild fatigue and nausea were reported in 9 (17.3%) and 6 (11.5%) patients, respectively. One instance of grade 5 toxicity was observed. Two patients (1.5%) had grade 2 gastric ulcers. No other grade ≥3 gastrointestinal toxicities occurred. CONCLUSIONS: Repeated SBRT is feasible and produces minimal toxicity in patients with HCC and Child-Pugh scores of ≤7 and a low normal liver dose.

Usefulness of virtual touch tissue quantification for predicting the presence of esophageal varices in patients with liver cirrhosis.

BACKGROUND AND AIM: Measuring the hepatic venous pressure gradient (HVPG) is an established technique to detect increased portal pressure and predict the presence of esophageal varices (EVs); however, the risk of the test is greater than the information it provides. This study aimed to clarify the usefulness of virtual touch tissue quantification (VTQ), which assesses liver stiffness, in predicting the presence of EVs in patients with liver cirrhosis by comparing it with HVPG. METHODS: Two hundred seventeen patients with liver cirrhosis underwent VTQ, HVPG measurement, and upper endoscopy. Patients were divided into three groups: group V, hepatitis C virus liver cirrhosis (n = 40); group A, alcoholic liver cirrhosis (n = 116); and group N, other liver cirrhosis (n = 61). In each group, we performed linear regression analysis of VTQ and HVPG data. The accuracy of VTQ and HVPG measurement in predicting the presence of EVs and high-risk EVs (EV category F2 and F3) was assessed by area under the receiver operating characteristic curve (AUROC). RESULTS: VTQ was significantly correlated with the HVPG in the whole patients and in each group, and both VTQ and HVPG values were significantly higher in patients with EVs and high-risk EVs than in those without. The AUROC for the presence of EVs for VTQ was 0.76 in the whole sample, 0.76 in group V, 0.79 in group A, and 0.67 in group N; and for HVPG, 0.92, 0.94, 0.93, and 0.88, respectively. For VTQ, the AUROC for the presence of high-risk EVs was 0.78 in the whole sample, 0.78 in group V, 0.73 in group A, and 0.73 in group N; and for HVPG, it was 0.85, 0.82, 0.85, and 0.82, respectively. CONCLUSION: VTQ was reliable at predicting the presence of EVs and high-risk EVs. Therefore, we propose that VTQ is a useful, noninvasive tool for predicting the presence of EVs in daily medical care.

Mutated GM-CSF-based CAR-T cells targeting CD116/CD131 complexes exhibit enhanced anti-tumor effects against acute myeloid leukaemia.

OBJECTIVES: As the prognosis of relapsed/refractory (R/R) acute myeloid leukaemia (AML) remains poor, novel treatment strategies are urgently needed. Clinical trials have shown that chimeric antigen receptor (CAR)-T cells for AML are more challenging than those targeting CD19 in B-cell malignancies. We recently developed piggyBac-modified ligand-based CAR-T cells that target CD116/CD131 complexes, also known as the GM-CSF receptor (GMR), for the treatment of juvenile myelomonocytic leukaemia. This study therefore aimed to develop a novel therapeutic method for R/R AML using GMR CAR-T cells. METHODS: To further improve the efficacy of the original GMR CAR-T cells, we have developed novel GMR CAR vectors incorporating a mutated GM-CSF for the antigen-binding domain and G4S spacer. All GMR CAR-T cells were generated using a piggyBac-based gene transfer system. The anti-tumor effect of GMR CAR-T cells was tested in mouse AML xenograft models. RESULTS: Nearly 80% of the AML cells predominant in myelomonocytic leukaemia were found to express CD116. GMR CAR-T cells exhibited potent cytotoxic activities against CD116+ AML cells in vitro. Furthermore, GMR CAR-T cells incorporating a G4S spacer significantly improved long-term in vitro and in vivo anti-tumor effects. By employing a mutated GM-CSF at residue 21 (E21K), the anti-tumor effects of GMR CAR-T cells were also improved especially in long-term in vitro settings. Although GMR CAR-T cells exerted cytotoxic effects on normal monocytes, their lethality on normal neutrophils, T cells, B cells and NK cells was minimal. CONCLUSIONS: GMR CAR-T cell therapy represents a promising strategy for CD116+ R/R AML.

Endoscopic snare excision of a major duodenal papillary tumor.

BACKGROUND/AIMS: Tumors of the duodenal papilla include hyperplasia, adenoma, carcinoma in adenoma, and carcinoma. Since the duodenal papilla has special anatomical characteristics and treatment involves major intervention, a correct preoperative diagnosis is essential for successful treatment. METHODS: In patients with adenoma or early carcinoma of the papilla, endoscopic snare excision is indicated for complete removal of the tumor. Postoperative pancreatitis and cholangitis are major complications of endoscopic techniques, and we describe here in detail our procedure aiming to reduce the incidence of such complications. RESULTS: Endoscopic snare excision of a tumor of the major duodenal papilla was carried out in 36 patients. Bleeding after endoscopic excision occurred in 6 cases (17%), postoperative pancreatitis in 11 cases (30%), and postoperative cholecystitis in 1 case (3%). All patients recovered from the complications within 1 week. CONCLUSION: Our results suggest that the procedure for endoscopic snare excision used to resect major papillary tumors is safe and helps to prevent serious complications.

Magnitude and direction of stream-forest community interactions change with timescale.

Networks of direct and indirect biotic interactions underpin the complex dynamics and stability of ecological systems, yet experimental and theoretical studies often yield conflicting evidence regarding the direction (positive or negative) or magnitude of these interactions. We revisited pioneering data sets collected at the deciduous forested Horonai Stream and conducted ecosystem-level syntheses to demonstrate that the direction of direct and indirect interactions can change depending on the timescale of observation. Prior experimental studies showed that terrestrial prey that enter the stream from the adjacent forest caused positive indirect effects on aquatic invertebrates during summer by diverting fish consumption. Seasonal and annual estimates of secondary production and organic matter flows along food web pathways demonstrate that this seasonal input of terrestrial invertebrate prey increases production of certain fish species, reversing the indirect effect on aquatic invertebrates from positive at the seasonal timescale to negative at the annual timescale. Even though terrestrial invertebrate prey contributed 54% of the annual organic matter flux to fishes, primarily during summer, fish still consumed 98% of the aquatic invertebrate annual production, leading to top-down control that is not revealed in short-term experiments and demonstrating that aquatic prey may be a limiting resource for fishes. Changes in the direction or magnitude of interactions may be a key factor creating nonlinear or stabilizing feedbacks in complex systems, and these dynamics can be revealed by merging experimental and comparative approaches at different scales.

Identification of tumor promotion marker genes for predicting tumor promoting potential of chemicals in BALB/c 3T3 cells.

Tumor promoters can cause development of tumors in initiated cells and the majority of them are non-genotoxic carcinogens. The detection of tumor promoters is important for the prevention of cancer. The in vitro two-stage transformation assay, using BALB/c 3T3 cells, is a useful system, and benefits from a convenient protocol and high predictability of mammalian carcinogenicity. But these assays are time-consuming and often require expertise for microscopic observation. To construct an in vitro tumor promoting activity test system, we performed large-scale gene expression analyses, using DNA microarrays, of BALB/c 3T3 cells following treatment with nine chemicals that are known to induce tumor promotion: TPA, zinc chloride, sodium orthovanadate, okadaic acid, insulin, lithocolic acid, phenobarbital sodium, sodium saccharide, sodium arsenite. As a result of DNA microarray and real time PCR analyses, 22 marker genes were identified. These consisted of genes related to cell cycle, regulation of transcription, anti-apoptosis, and positive regulation of cell proliferation. There was a correlation between these 22 marker genes and the cell transformation assay results in BALB/c 3T3 cells. These results suggest that this tumor promoting activity test system, based on 22 marker genes, can become a valuable tool for screening potential tumor promoters.

Reactivity of shrimp allergy-related IgE antibodies to krill tropomyosin.

BACKGROUND: Krill, which morphologically resembles small shrimp, represents small ocean crustaceans and has been used for human consumption in Japan and some other countries. The major allergen in crustaceans has been reported to be tropomyosin, but the allergenicity of krill tropomyosin remains uncertain. METHODS: Amino acid sequences of tropomyosin in two species of krill (Euphausia superba and E. pacifica) were deduced. Recombinant krill tropomyosins were produced in Escherichia coli using a pCold IV vector system, and the cross-reactivity of shrimp allergy-related IgE to the recombinant tropomyosins and several animal protein extracts was assessed by immunoblotting. RESULTS: The deduced amino acid sequences of the E. superba and E. pacifica tropomyosins (designated as Eup s 1 and Eup p 1, respectively) were 284 residues and showed significant homology to those of shrimp, lobster and crab tropomyosins. Shrimp allergy-related IgE reacted to approximately 38-kDa protein bands in krill (E. superba), shrimp, lobster and crab protein extracts but did not react to protein extracts from either mollusks or vertebrates. Furthermore, the IgE recognized rEup s 1 and rEup p 1 as 38-kDa protein bands, and absorption of the IgE with rEup s 1 removed IgE reactivity to recombinant tropomyosins and protein extracts from krill and shrimp. CONCLUSIONS: Krill tropomyosins included highly homologous sequences to previously reported IgE-binding epitopes in Pen a 1 (tropomyosin of Penaeus aztecus). The cross-reactivity in shrimp allergy-related IgE binding among krill, shrimp, lobster and crab tropomyosins was revealed. These observations suggest the potential allergenicity of krill tropomyosin.

Orally active factor Xa inhibitors: investigation of a novel series of 3-amidinophenylsulfonamide derivatives using an amidoxime prodrug strategy.

A series of novel and potent 3-amidinophenylsulfonamide derivatives of factor Xa inhibitors were designed and synthesized using an amidoxime prodrug strategy. We focused on systemic clearance of parent compounds in rats, and performed in vivo pharmacokinetic screening. Incorporation of a carboxymethoxy group markedly improved systemic clearance (compound 43), and the related amidoxime 44 showed sufficient prodrug conversion. Compound 45, the double prodrug of 43, exhibited practicable bioavailability after oral administration in rats. Among the various compounds under investigation, KFA-1982 was selected for clinical development.

Bezafibrate prevents hepatic stellate cell activation and fibrogenesis in a murine steatohepatitis model, and suppresses fibrogenic response induced by transforming growth factor-beta1 in a cultured stellate cell line.

AIM: The aim of this study was to investigate the preventive actions of bezafibrate against non-alcoholic steatohepatitis (NASH), the activation of hepatic stellate cells (HSC), and fibrogenesis by using a model of NASH and an in vitro model. METHODS: Male KK-A(y)/TaJcl (KK-A(y)) mice were fed a methionine and choline-deficient (MCD) diet or a MCD diet containing bezafibrate or pioglitazone for 7 weeks, after which biochemical parameters, pathological changes, and hepatic mRNA levels were assessed. An in vitro HSC model was designed by using a previously described RI-T cell line stimulated by transforming growth factor-beta1 (TGF-beta1). RESULTS: MCD diet-fed KK-A(y) mice developed hepatic steatosis, oxidative stress, inflammation, and hepatic fibrosis. Bezafibrate markedly decreased the hepatic content of triglyceride accumulation of fatty droplets within hepatocytes, and increased the expression of hepatic fatty acid beta-oxidative genes in MCD diet-fed KK-A(y) mice. Bezafibrate markedly inhibited the increases in the plasma alanine aminotransferase level and hepatic content of thiobarbituric acid-reactive substances in this model. Moreover, it dramatically reduced hepatic inflammatory changes and fibrosis concomitantly with marked reductions in the mRNA levels for inflammatory cytokine, chemokine, and profibrogenic genes. Importantly, both bezafibrate and pioglitazone markedly reduced the mRNA levels of profibrogenic and fibrogenic genes in TGF-beta1-stimulated cells. CONCLUSION: Bezafibrate improved hepatic steatosis and potently prevented inflammation, oxidative stress, HSC activation, and fibrogenesis in the liver. Moreover, this study was the first to demonstrate that bezafibrate directly inhibits hepatic fibrogenic response induced by TGF-beta1 in vitro. Hence bezafibrate may be a new therapeutic strategy against NASH and hepatic fibrosis.

Analysis of proteins responsive to acetic acid in Acetobacter: molecular mechanisms conferring acetic acid resistance in acetic acid bacteria.

Acetic acid bacteria are used for industrial vinegar production because of their remarkable ability to oxidize ethanol and high resistance to acetic acid. Although several molecular machineries responsible for acetic acid resistance in acetic acid bacteria have been reported, the entire mechanism that confers acetic acid resistance has not been completely understood. One of the promising methods to elucidate the entire mechanism is global analysis of proteins responsive to acetic acid by two-dimensional gel electrophoresis. Recently, two proteins whose production was greatly enhanced by acetic acid in Acetobacter aceti were identified to be aconitase and a putative ABC-transporter, respectively; furthermore, overexpression or disruption of the genes encoding these proteins affected acetic acid resistance in A. aceti, indicating that these proteins are involved in acetic acid resistance. Overexpression of each gene increased acetic acid resistance in Acetobacter, which resulted in an improvement in the productivity of acetic acid fermentation. Taken together, the results of the proteomic analysis and those of previous studies indicate that acetic acid resistance in acetic acid bacteria is conferred by several mechanisms. These findings also provide a clue to breed a strain having high resistance to acetic acid for vinegar fermentation.

Japanese mothers' prebirth Adult Attachment Interview predicts their infants' response to the Strange Situation Procedure: The strange situation in Japan revisited three decades later.

The current study investigated the intergenerational transmission of attachment in Sapporo, Japan, using the Adult Attachment Interview (AAI) and the Strange Situation Procedure (SSP). This is the first SSP study in Sapporo in three decades, after a study in the mid-1980s reported controversial results. The SSP distributions found in the current study, however, were similar to those reported in the earlier Sapporo study, including its controversial finding that ambivalent attachment was predominant in insecure infants. The current study used the AAI and the SSP to study the intergenerational transmission of attachment in Japan and found a strong categorical match consistent with those reported elsewhere in the world. A proportion of infants who were judged disorganized as the first report in this Japanese sample was also found to be similar to the reported global norm. Disorganized attachment in Japanese infants was strongly predicted by the mother's unresolved state of mind as was found across normative samples. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

One-step purification of histone deacetylase from Escherichia coli cell-lysate by counter-current chromatography using aqueous two-phase system.

Aqueous-aqueous two-phase (AATP) systems composed of polyethylene glycol (PEG) (molecular mass, M(r):1000-8000) and dextran (M(r):40,000) were evaluated for purification of maltose binding protein tagged-histone deacetylase (MBP-HDAC) by counter-current chromatography (CCC). CCC purification of an MBP-HDAC from Escherichia coli cell-lysate was successfully demonstrated with a 7.0% PEG 3350-10% dextran T40 system containing 10 mM potassium phosphate buffer at pH 9.0. After CCC purification, both polymers in the CCC fractions were easily removed by ultrafiltration in a short period of time. The collected fractions containing target protein were analyzed by an HPLC-based in vitro assay as well as sodium dodecyl sulfate polyacrylamide gel electrophoresis. MBP tag was digested from fusion HDAC during the CCC separation and native HDAC was purified by one-step operation with well preserved deacetyl enzyme activity.

Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.

We evaluated the effects of bezafibrate, a peroxisome proliferator-activated receptor (PPAR) pan-agonist, and GW501516, a PPARdelta agonist, on mice fed a methionine- and choline-deficient (MCD) diet, a model of non-alcholic steatohepatitis (NASH), to investigate (a) the efficacy of bezafibrate against non-alcholic steatohepatitis and (b) the relation between non-alcholic steatohepatitis and the functional role of PPARdelta. Bezafibrate (50 or 100 mg/kg/day) and GW501516 (10 mg/kg/day) were administered by gavage once a day for 5 weeks. Hepatic lipid contents, plasma triglyceride, high density lipoprotein (HDL)-cholesterol and alanine aminotransferase (ALT) concentrations were evaluated, as were histopathological changes in the liver and hepatic mRNA expression levels. Bezafibrate and GW501516 inhibited the MCD-diet-induced elevations of hepatic triglyceride and thiobarbituric acid-reactants contents and the histopathological increases in fatty droplets within hepatocytes, liver inflammation and number of activated hepatic stellate cells. In this model, bezafibrate and GW501516 increased the levels of hepatic mRNAs associated with fatty acid beta-oxidation [acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-1 (CPT-1), liver-fatty acid binding protein (L-FABP) and peroxisomal ketothiolase], and reduced the levels of those associated with inflammatory cytokines or chemokine [transforming growth factor (TGF)-beta1, interleukin (IL)-6, IL-1beta, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF) alpha and nuclear factor (NF)-kappaB1]. In addition, bezafibrate characteristically reduced the elevation in the level of plasma ALT, but enhanced that in plasma adiponectin and increased the mRNA expression levels of its receptors (adiponectin receptors 1 and 2). These results suggest that (a) bezafibrate (especially) and GW501516 might improve hepatic steatosis via an improvement in fatty acid beta-oxidation and a direct prevention of inflammation, (b) treatment with a PPARdelta agonist might improve non-alcholic steatohepatitis, (c) bezafibrate may improve non-alcholic steatohepatitis via activation not only of PPARalpha but also of PPARdelta, because bezafibrate is a PPAR pan-agonist.