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Chromosome-wide late replication is an enigmatic hallmark of the inactive X chromosome (Xi). How it is established and what it represents remains obscure. By single-cell DNA replication sequencing, here we show that the entire Xi is reorganized to replicate rapidly and uniformly in late S-phase during X-chromosome inactivation (XCI), reflecting its relatively uniform structure revealed by 4C-seq. Despite this uniformity, only a subset of the Xi became earlier replicating in SmcHD1-mutant cells. In the mutant, these domains protruded out of the Xi core, contacted each other and became transcriptionally reactivated. 4C-seq suggested that they constituted the outermost layer of the Xi even before XCI and were rich in escape genes. We propose that this default positioning forms the basis for their inherent heterochromatin instability in cells lacking the Xi-binding protein SmcHD1 or exhibiting XCI escape. These observations underscore the importance of 3D genome organization for heterochromatin stability and gene regulation.

In female mammals, one of the two X chromosomes becomes inactivated during development by X-chromosome inactivation (XCI). Although Polycomb repressive complex (PRC) 1 and PRC2 have both been implicated in gene silencing, their exact roles in XCI during in vivo development have remained elusive. To this end, we have studied mouse embryos lacking either PRC1 or PRC2. Here we demonstrate that the loss of either PRC has a substantial impact on maintenance of gene silencing on the inactive X chromosome (Xi) in extra-embryonic tissues, with overlapping yet different genes affected, indicating potentially independent roles of the two complexes. Importantly, a lack of PRC1 does not affect PRC2/H3K27me3 accumulation and a lack of PRC2 does not impact PRC1/H2AK119ub1 accumulation on the Xi. Thus PRC1 and PRC2 contribute independently to the maintenance of XCI in early post-implantation extra-embryonic lineages, revealing that both Polycomb complexes can be directly involved and differently deployed in XCI.

ABSTRACTWe investigated the anti-stress effect of rosemary (Rosmarinus officinalisL.) leaf extract (RLE) on restraint-stressed mice and found that RLE alleviated decreases in the number of intestinal goblet cells and amount of hepatic triglycerides. It also decreased the immobility time in the forced-swimming test and activation of microglia in the brain, suggesting that RLE has beneficial effects on stress-induced dysfunctions.

ABSTRACTKoji, which is manufactured by proliferating non-pathogenic fungus Aspergillus oryzaeon steamed rice, is the base for Japanese traditional fermented foods. We have revealed that kojiand related Japanese fermented foods and drinks such as amazake, shio-koji, unfiltered sake and miso contain abundant glycosylceramide. Here, we report that feeding of kojiglycosylceramide to obese mice alters the cholesterol metabolism . Liver cholesterol was significantly decreased in obese mice fed with kojiglycosylceramide. We hypothesized that their liver cholesterol was decreased because it was converted to bile acids. Consistent with the hypothesis, many bile acids were increased in the cecum and feces of obese mice fed with kojiglycosylceramide. Expressions of CYP7A1 and ABCG8 involved in the metabolism of cholesterol were significantly increased in the liver of mice fed with kojiglycosylceramide. Therefore, it was considered that kojiglycosylceramide affects the cholesterol metabolism in obese mice.

Here, we report a single-cell DNA replication sequencing method, scRepli-seq, a genome-wide methodology that measures copy number differences between replicated and unreplicated DNA. Using scRepli-seq, we demonstrate that replication-domain organization is conserved among individual mouse embryonic stem cells (mESCs). Differentiated mESCs exhibited distinct profiles, which were also conserved among cells. Haplotype-resolved scRepli-seq revealed similar replication profiles of homologous autosomes, while the inactive X chromosome was clearly replicated later than its active counterpart. However, a small degree of cell-to-cell replication-timing heterogeneity was present, which was smallest at the beginning and the end of S phase. In addition, developmentally regulated domains were found to deviate from others and showed a higher degree of heterogeneity, thus suggesting a link to developmental plasticity. Moreover, allelic expression imbalance was found to strongly associate with replication-timing asynchrony. Our results form a foundation for single-cell-level understanding of DNA replication regulation and provide insights into three-dimensional genome organization.

Here, Terui et al. studied the mechanisms underlying chromatin remodeling that occurs during MMR. They show that the eukaryotic MMR system has an ability to exclude local nucleosomes and identify Smarcad1/Fun30 as an accessory factor for the MMR reaction.

DNA double-strand breaks (DSBs) are repaired by either the homology-directed repair (HDR) or the non-homologous end-joining (NHEJ) pathway. RIF1 (RAP1-interacting factor homolog) was recently shown to stimulate NHEJ through an interaction with 53BP1 (p53-binding protein 1) phosphorylated at S/TQ sites, but the molecular mechanism underlying pathway choice remains unclear. Here, we show that SCAI (suppressor of cancer cell invasion) binds to 53BP1 phosphorylated at S/TP sites and facilitates HDR. Upon DNA damage, RIF1 immediately accumulates at damage sites and then gradually dissociates from 53BP1 and is subsequently replaced with SCAI. Depletion of SCAI reduces both the accumulation of HDR factors, including BRCA1 (breast cancer susceptibility gene 1), at damage sites and the efficiency of HDR, as detected by a reporter assay system. These data suggest that SCAI inhibits RIF1 function to allow BRCA1-mediated repair, which possibly includes alt-NHEJ and resection-dependent NHEJ in G1, as well as HDR in S/G2.

This study aimed to establish variants in CBX1, encoding heterochromatin protein 1β (HP1β), as a cause of a novel syndromic neurodevelopmental disorder.

Steviol glycosides obtained from Stevia rebaudianaleaves are increasingly used in the food industry as natural low-calorie sweeteners. Among them, the sweetness of major glycosides composed of glucose residues (e.g., stevioside and rebaudioside A) has been widely studied. However, the properties of minor natural products containing rhamnose or xylose residues are poorly investigated. In this study, five unreported steviol glycosides containing rhamnose or xylose were extracted from our developing stevia leaves, and their sweetness was evaluated. The highly glycosylated steviol glycosides were identified, and their structures were examined by fragmentation analysis using mass spectrometry. Chemical synthesis of these glycosides confirmed their structures and allowed sensory evaluation of minor steviol glycosides. Our study revealed that a xylose-containing glycoside, rebaudioside FX1, exhibits a well-balanced sweetness, and thus, it is a promising candidate for natural sweeteners used in the food industry.

Many animal studies on improvement of lipid metabolism, using dietary components, fast the animals on the final day of the feeding. Although fasting has a significant impact on lipid metabolism, its time-dependent influence is not fully understood. We examined the effects of several fasting times on lipid metabolism. Rats fed with a semisynthetic diet for 2 wk were killed after 0 (9:00 am), 6 (7:00 am–1:00 pm), 9 (0:00 am–9:00 am), and 13 h (8:00 pm–9:00 am) of fasting. Compared to the 0 h group, marked reduction of liver weight and hepatic triacylglycerol content was observed in the 9 and 13 h groups. Activities of hepatic enzymes involved in fatty acid synthesis gradually decreased during fasting. In contrast, drastic time-dependent reduction of gene expression, of the enzymes, was observed. Expression of carnitine palmitoyltransferase mRNA was higher in the fasting groups than in the 0 h group. Our study showed that fasting has a significant impact on several parameters related to lipid metabolism in rat liver.

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. The discovery of food components that would ameliorate NAFLD is therefore of interest. Lotus root, the edible rhizome of Nelumbo nucifera, contains a high level of polyphenolic compounds, and several health-promoting properties of lotus root have been reported. The present study examines whether dietary lotus root powder can protect db/dbmice from hepatic injury. After 3 weeks of feeding, the hepatomegaly, hepatic triglyceride accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in the Lotus diet-fed db/dbmice relative to the control mice. These effects were partly attributable to suppression of the lipogenic enzyme activities and mRNA expression by the Lotus diet. The serum levels of adiponectin, which has been reported to have a protective effect against NAFLD, were significantly higher in the Lotus group than in the Control group of the db/dbmice. Moreover, the hepatic expression of such inflammatory genes as tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were markedly suppressed by the Lotus diet. We speculate that the development and progression of NAFLD were prevented by suppressing the expression of lipogenic and inflammatory genes as a result of the higher serum adioponectin level in the Lotus diet-fed db/dbmice.

Clinical studies were conducted to investigate the pharmacokinetics of roxatidine acetate hydrochloride capsules (ALTAT® CAPSULES) in children. In a single-dose pharmacokinetic (PK) study in pediatric patients aged between 6 and 14 years with acid-related diseases, 37.5mg or 75mg roxatidine capsules were given orally, and blood samples were collected to determine the plasma roxatidine concentrations. Meanwhile, a single-dose PK study in healthy adult volunteers was newly conducted; subjects were given 37.5 mg, 75 mg or 150 mg roxatidine capsules. Differences were present between the PK parameters in pediatric patients and those in healthy adult volunteers. However, the CL/F and Vd/F adjusted by body surface area (BSA) or body weight (BW) were comparable. A close correlation of the Cmaxand AUC0-∞to the dose per unit BSA (mg/m2) or BW (mg/kg) was also shown. In the multiple-dose study in pediatric patients, no roxatidine accumulation in plasma was observed, as was the case with a previous study in adults. These data show that the PK profile of roxatidine in pediatric patients is similar to the profile in healthy adult volunteers when adjusted by BSA or BW.

The effects were compared of T0901317, a liver X receptor agonist, on deposition in the liver and serum and lymphatic absorption of plant sterols in stroke-prone spontaneously hypertensive rats (SHRSPs) having a missense mutation in Abcg5, which codes for ATP-binding cassette transporter (ABC) G5, with those in Wistar rats. Both strains were pair-fed for 7 d with a 0.5% plant sterol diet with or without 5 mg/kg of body weight of T0901317. The deposition of plant sterols in the liver and serum was higher in SHRSPs than in Wistar rats. A significant reduction of plant sterol deposition was observed in Wistar rats, but not in SHRSPs when T0901317 was given. Both strains were then fed for 7 d with a control diet with or without T0901317. The lymphatic absorption of plant sterols was reduced to almost half the normal level by the T0901317 treatment. However, no difference in absorption was apparent between SHRSPs and Wistar rats regardless of the T0901317 treatment. These results suggest that the plant sterol deposition in SHRSPs was not necessarily caused by the increased absorption of plant sterols.

The effects of a hot water extract and fractional extracts from rabbiteye blueberry (Vaccinium ashei reade) leaves (BBL) on lipid metabolism were studied in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Feeding the hot water extract and fractional extracts from BBL alleviated hepatic triglyceride accumulation in the rats. Additionally, feeding with the flavonol glycoside (FG) and proanthocyanidin (PA) fractions lowered serum cholesterol levels in the obese rats. The results from measurements of the hepatic enzyme activity indicate that the hypolipidemic effects of the hot water extract and the PA fraction might be attributable to enhanced lipolysis in the liver. The reduced serum levels of C-reactive protein, an inflammatory cytokine, by the chlorogenic acid + rutin fraction and FG fraction might be associated with alleviating the metabolic abnormalities in obese rats. These results indicate that the BBL extracts, and especially FG and PA, exerted hypolipidemic effects on obese OLETF rats and suggest that an infusion of BBL can be useful as a dietary hypolipidemic component.

Study of the essential roles of CDK in initiation of DNA replication in fission yeast indicates that CDK phosphorylates Sld3 and Drc1/Sld2 and promotes their interactions with Cut5, which are required for origin loading of Cut5. Thus CDK regulates assembly of replication factors onto origins by promoting ternary Sld3–Cut5–Drc1 complex formation.

Cyclin-dependent kinase (CDK) plays essential roles in the initiation of DNA replication in eukaryotes. Although interactions of CDK-phosphorylated Sld2/Drc1 and Sld3 with Dpb11 have been shown to be essential in budding yeast, it is not known whether the mechanism is conserved. In this study, we investigated how CDK promotes the assembly of replication proteins onto replication origins in fission yeast. Phosphorylation of Sld3 was found to be dependent on CDK in S phase. Alanine substitutions at CDK sites decreased the interaction with Cut5/Dpb11 at the N-terminal BRCT motifs and decreased the loading of Cut5 onto replication origins. This defect was suppressed by overexpression of drc1+. Phosphorylation of a conserved CDK site, Thr-111, in Drc1 was critical for interaction with Cut5 at the C-terminal BRCT motifs and was required for loading of Cut5. In a yeast three-hybrid assay, Sld3, Cut5, and Drc1 were found to form a ternary complex dependent on the CDK sites of Sld3 and Drc1, and Drc1–Cut5 binding enhanced the Sld3–Cut5 interaction. These results show that the mechanism of CDK-dependent loading of Cut5 is conserved in fission yeast in a manner similar to that elucidated in budding yeast.

The effects of blueberry leaf (BBL) on lipid metabolism were studied in obese rats. Feeding of BBL lowered levels of serum lipids and C-reactive protein and alleviated hepatic triglyceride accumulation in the rats. The hypolipidemic effect might be attributable to a reduction of lipogenesis and enhancement of lipolysis in the liver. These results suggest the use of blueberry leaf as a dietary hypolipidemic component.

Cohesin is a multiprotein complex essential for sister-chromatid cohesion. It plays a pivotal role in proper chromosome segregation and DNA damage repair. The mitotic behavior of cohesin is controlled through its phosphorylation, which possibly induces the dissociation of cohesin from chromosomes and enhances its susceptibility to separase. Here, we report using mass spectrometry and anti-phospho antibodies that the central domain of Rad21, the separase-target subunit of Schizosaccharomyces pombecohesin, is regulated by various kinase-induced phosphorylation at nine residues, indicating the multiple roles for S. pombe cohesin. In vegetative and non-dividing G0 cells, Rad21 is phosphorylated by unknown S/TP-consensus kinases, in mitotic and non-mitotic cells by polo/Plo1 and CDK, and in DNA-damaged cells by Rad3/ATR. While mitotic phosphorylation is implicated in the dissociation of Rad21 and its cleavage by separase in anaphase, the Rad3/ATR-dependent damage-induced phosphorylation occurs intensively at the time of repair completion, and only in post-replicative cells. This damage-induced Rad21 phosphorylation is involved in the recovery process of cells from checkpoint arrest, and needed for the removal of cohesin by separase after the completion of damage repair. These complex phospho-regulations of Rad21 indicate the functional significance of cohesin in cell adaptation to a variety of cellular conditions.

Sister chromatid separation requires two steps of proteolysis. Securin, the chaperon and inhibitor of separase, is destructed in anaphase after polyubiquitination, and resulting activated separase cleaves the cohesin subunit Scc1/Rad21. Fission yeast securin/Cut2 and separase/Cut1 that form the complex are essential for viability and a number of temperature-sensitive (ts) mutants have been isolated. We here report that the stresses such as 1.2 M sorbitol, 0.6 M KCl and 0.1 M CaCl2 in the medium suppress the ts phenotypes of all the cut1 mutants and two of the three cut2 mutants examined. This unexpected finding led us to study how the ts phenotypes of cut1 and cut2 mutants were rescued by the increased stresses. The stresses caused a temporal arrest in the cell number increase, and this arrest was dependent on Spc1/Sty1 but not Rad3 and Mad2. During the 2-3 hr arrested period that occurred prior to the re-start of division cycle, the level of securin dramatically increased, apparently accompanying the increased complex formation with mutant separase protein. Securin bound to separase was hyperphosphorylated. The stresses could not rescue the indestructible Cut2 and Rad21 mutants. We postulate that the stresses produce the hyperchaperonic form of Cut2 that can rescue separase mutations.

This study was performed to examine the effect of consumption of pork-liver protein hydrolysate (PLH) on body fat accumulation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a non-insulin-dependent diabetes mellitus model and in Long-Evans Tokushima Otsuka (LETO) rats as a control. Male 20-week-old OLETF and LETO rats were pair-fed either PLH or casein containing diet for 14 weeks. In the OLETF rats, dietary PLH significantly reduced the growth and weight of fat pad including perirenal and epididymal adipose tissues. Consumption of PLH markedly suppressed hepatic activities of lipogenesis enzymes such as glucose-6-phosphate dehydrogenase and fatty acid synthase and slightly elevated fecal excretion of total fat. In the LETO rats, growth and adipose tissue weight were unaffected by dietary treatment. The results suggest that PLH is a novel ingredient suppressing body fat in genetically obese rats by reducing lipogenesis.

Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biologic effects both in vitroand in vivo. Our results clearly show the specific action of the 10trans,12cis-CLA isomer against hyperlipidemia and obesity in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks of feeding with 10t,12c-CLA, but not 9cis,11trans-CLA, abdominal adipose tissue weight and serum and hepatic lipid levels in OLETF rats were lower than those in linoleic acid-fed rats. These effects were attributable to suppressed fatty acid synthesis and enhanced fatty acid beta oxidation in the liver on a 10t,12c-CLA diet. Additionally, we showed that mRNA expression of fatty acid synthase, carnitine palmitoyltransferase, leptin, and sterol regulatory element binding protein-1 was also regulated by 10t,12c-CLA. We suppose that 10t,12c-CLA reveals hypolipidemic and anti-obese activity through the alteration of mRNA expressions in the liver and white adipose tissue.

Tea catechins, rich in (−)-epigallocatechin gallate and (−)-epicatechin gallate, or heat-treated tea catechins in which about 50% of the (−)-epigallocatechin gallate and (−)-epicatechin gallate in tea catechins was epimerized to (−)-gallocatechin gallate and (−)-catechin gallate, were fed to rats at 1% level for 23 d. Visceral fat deposition and the concentration of hepatic triacylglycerol were significantly lower in the tea catechin and heat-treated tea catechin groups than in the control group. The activities of fatty acid synthase and the malic enzyme in the liver cytosol were significantly lower in the two catechin groups than in the control group. In contrast, the activities of carnitine palmitoyltransferase and acyl-CoA oxidase in the liver homogenate were not significantly different among the three groups. These results suggest that the reduction in activities of enzymes related to hepatic fatty acid synthesis by the feeding of tea catechins or heat-treated tea catechins can cause reductions of hepatic triacylglycerol and possibly of visceral fat deposition.

Background: Among various alcoholic beverages, it has reported that beer has a potent activity to stimulate gastric emptying. Our previous studies showed that beer congener stimulated gastrointestinal motility by directly stimulating muscarinic M3receptor, present in smooth muscles of the gastrointestinal tract. However, active components that account for the action have yet to be identified. We attempted to isolate the stimulant(s) of gastrointestinal motility in beer.

A mixture of conjugated linoleic acids (CLAs) was prepared by alkali conjugation of high purity linoleic acid. The preparation contained 45.1 wt% cis-9, trans-11 (c9,t11)-CLA, 46.8 wt% trans-10, cis-12 (t10,c12)-CLA, and 5.3 wt% other CLAs. A process comprising Candida rugosalipase-catalyzed selective esterification with lauryl alcohol, molecular distillation, and urea adduct fractionation under strict conditions in ethanol was very effective for purification of c9,t11- and t10,c12-CLAs. In particular, the urea adduct fractionation efficiently eliminated CLAs except c9,t11- and t10,c12-isomers. Purification of c9,t11- and t10,c12-CLAs from 1.0 kg of the CLA mixture increased the c9,t11-CLA purity to 93.1% with 34% recovery of the initial content, and increased the t10,c12-CLA purity to 95.3% with 31% recovery.

The hypocholesterolemic effect of rice bran oil (RBO) is defined in human and animal experiments which indicate the presence of active component(s) in the unsaponifiable fraction, but the detailed mechanism is not known yet. Exogenously hypercholesterolemic (ExHC) rats were fed for 2 weeks on a 0.5% cholesterol diet supplemented with 10% each of RBO, RBO-simulated oil (RBOSO) in its fatty acid composition, or RBOSO plus 0.25% unsaponifiable compounds (UC) from RBO. Rats fed RBO or the UC resulted in lowing serum and liver cholesterol concentration and preventing reduction of high density lipoproteinic-cholesterol. Dietary RBO or the UC led to an elevation of fecal neutral sterol excretion, but no significant change in fecal bile acid excretion or in hepatic abundance of mRNAs for 3-hydroxy-3-methylglutaryl-CoA reductase, cholesterol-7α-hydroxylase, and low density lipoprotein receptor. Besides, serum and liver α-tocopherol concentrations were lowered in RBO or the UC-fed rats. These results show that the UC in RBO leads to a decreased serum cholesterol concentration by interrupting the absorption of intestinal hydrophobic compounds rather than by modifying cholesterol metabolism in the liver.

For monitoring chemical processes, multivariate statistical process control (MSPC) has been widely used. In the present work, a new process monitoring method is proposed. The proposed method utilizes a change in distribution of process data, since the distribution reflects the corresponding operating condition. In order to quantitatively evaluate the difference between two data sets, the dissimilarity index is defined. The proposed method and the conventional SPC methods are applied to monitoring problems of the Tennessee Eastman process. The results have clearly shown that the monitoring performance of the proposed method is considerably better than that of the conventional methods.

The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD rats with a high response to dietary cholesterol. To understand the underlying mechanism(s) for this hypercholesterolemia, the interactive effects of dietary fatty acid and the susceptibility of rats to dietary cholesterol on the serum cholesterol concentration and hepatic mRNA abundance of the low-density lipoprotein (LDL) receptor, cholesterol 7α-hydroxylase (7α-hydroxylase) and 3-hydroxyl-3methyl-glutaryl (HMG) CoA reductase were examined. Both strains were fed on a diet supplemented with 10% each of olive, safflower or coconut oil with or without the addition of 1% cholesterol for one week. The ExHC rats fed on olive, safflower and coconut oil in combination with cholesterol respectively resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than that in the animals fed on the corresponding dietary fats without any supplementation of cholesterol (p<0.01 by dietary cholesterol or type of fat). The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC rats fed on the safflower oil-containing diet supplemented with cholesterol resulted in a higher mRNA abundance of the LDL receptor and 7α-hydroxylase than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no dietary cholesterol-dependent change of mRNA abundance in either strain fed on olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL receptor and of 7α-hydroxylase depended on the dietary combination of cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may alleviate exogenous hypercholesterolemia by activating the process involved in the hepatic uptake and biliary excretion of serum cholesterol.

Multivariate statistical process control (MSPC) has been successfully applied to chemical procesess. In order to improve the performance of fault detection, two kinds of advanced methods, known as moving principal component analysis (MPCA) and DISSIM, have been proposed. In MPCA and DISSIM, an abnormal operation can be detected by monitoring the directions of principal components (PCs) and the degree of dissimilarity between data sets, respectively. Another important extension of MSPC was made by using multiscale PCA (MS-PCA). In the present work, the characteristics of several monitoring methods are investigated. The monitoring performances are compared with using simulated data obtained from the Tennessee Eastman process. The results show that the advanced methods can outperform the conventional method. Furthermore, the advantage of MPCA and DISSIM over conventional MSPC (cMSPC) and that of the multiscale method are combined, and the new methods known as MS-MPCA and MS-DISSIM are proposed.

Exogenously hypercholesterolemic (ExHC) rats promptly increase serum cholesterol concentration in response to dietary cholesterol. To examine underlying mechanism(s) for this susceptibility, responses of mRNAs for cholesterol metabolism-related proteins and their activities in the liver to dietary cholesterol were compared between ExHC rats and their progenitor Sprague-Dawley rats. ExHC rats slightly decreased the abundance of low-density-lipoprotein (LDL) receptor mRNA in response to dietary cholesterol, although the amount of LDL receptor was not influenced. The abundance of cholesterol 7α-hydroxylase mRNA and the enzyme activity in response to dietary cholesterol were greater in ExHC rats, but the fecal excretion of bile acid was comparable between the strain. Dietary cholesterol-dependent elevation of acyl-CoA:cholesterol acyltransferase activity was greater in ExHC rats. The concentration of liver triacylglycerols was markedly lower in ExHC rats. These results suggest that ExHC rats may increase serum cholesterol by increasing hepatic secretion of cholesteryl ester-rich particles.

Atherosclerotic lesions of the thoracic aorta were induced in exogenously hypercholesterolemic (ExHC) rats by treating initially with hypervitamin D2and subsequently feeding on hypercholesterolemic diets for 180 days. Dietary soybean protein, in comparison with casein, substantially decreased the degree of atherosclerotic lesions, which was evaluated by intimai thickening, although with a similar topographical distribution. The casein-fed rats tended to maintain a high concentration of serum cholesterol, particularly in triacylglycerol-rich lipoproteins. The concentrations of apo A-I and TBARS in the serum was comparable between the dietary protein groups. The data suggest that dietary soybean protein, compared to casein, produced lipoproteins which were less atherosclerotic by partitioning cholesterol in the triacylglycerol-poor lipoproteins.

DNA double-strand breaks (DSBs) are repaired mainly by non-homologous end joining (NHEJ) or homologous recombination (HR). RIF1 negatively regulates resection through the effector Shieldin, which associates with a short 3′ single-stranded DNA (ssDNA) overhang by the MRN (MRE11-RAD50-NBS1) complex, to prevent further resection and HR repair. In this study, we show that RIF1, but not Shieldin, inhibits the accumulation of CtIP at DSB sites immediately after damage, suggesting that RIF1 has another effector besides Shieldin. We find that protein phosphatase 1 (PP1), a known RIF1 effector in replication, localizes at damage sites dependent on RIF1, where it suppresses downstream CtIP accumulation and limits the resection by the MRN complex. PP1 therefore acts as a RIF1 effector distinct from Shieldin. Furthermore, PP1 deficiency in the context of Shieldin depletion elevates HR immediately after irradiation. We conclude that PP1 inhibits resection before the action of Shieldin to prevent precocious HR in the early phase of the damage response.

The effects of soybean-derived phospholipid, PIPS NAGASETM(PIPS), on obesity-induced diseases were studied in obese rats. Dietary PIPS alleviated hepatomegaly and fatty liver in the rats. These effects were attributable to reduced lipogenesis and enhanced lipolysis in the liver. The results suggest that PIPS can be useful as a dietary component that would reduce the risk of lifestyle-related diseases.