Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor.

The emergence of acquired resistance is a major concern associated with molecularly targeted kinase inhibitors. The C797S mutation in the epidermal growth factor receptor (EGFR) confers resistance to osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI). We report that the derivatization of the marine alkaloid topoisomerase inhibitor lamellarin N provides a structurally new class of EGFR-TKIs. One of these, lamellarin 14, is effective against the C797S mutant EGFR. Bioinformatic analyses revealed that the derivatization transformed the topoisomerase inhibitor-like biological activity of lamellarin N into kinase inhibitor-like activity. Ba/F3 and PC-9 cells expressing the EGFR in-frame deletion within exon 19 (del ex19)/T790M/C797S triple-mutant were sensitive to lamellarin 14 in a dose range similar to the effective dose for cells expressing EGFR del ex19 or del ex19/T790M. Lamellarin 14 decreased the autophosphorylation of EGFR and the downstream signaling in the triple-mutant EGFR PC-9 cells. Furthermore, intraperitoneal administration of 10 mg/kg lamellarin 14 for 17 days suppressed tumor growth of the triple-mutant EGFR PC-9 cells in a mouse xenograft model using BALB/c nu/nu mice. Thus, lamellarin 14 serves as a novel structural backbone for an EGFR-TKI that prevents the development of cross-resistance against known drugs in this class.

Sox2 gene regulation via the D1 enhancer in embryonic neural tube and neural crest by the combined action of SOX2 and ZIC2.

The transcription factor (TF) SOX2 regulates various stem cells and tissue progenitors via functional interactions with cell type-specific partner TFs that co-bind to enhancer sequences. Neural progenitors are the major embryonic tissues where SOX2 assumes central regulatory roles. In order to characterize the partner TFs of SOX2 in neural progenitors, we investigated the regulation of the D1 enhancer of the Sox2 gene, which is activated in the embryonic neural tube (NT) and neural crest (NC), using chicken embryo electroporation. We identified essential TF binding sites for a SOX, and two ZIC TFs in the activation of the D1 enhancer. By comparison of dorso-ventral and antero-posterior patterns of D1 enhancer activation, and the effect of mutations on the enhancer activation patterns with TF expression patterns, we determined SOX2 and ZIC2 as the major D1 enhancer-activating TFs. Binding of these TFs to the D1 enhancer sequence was confirmed by chromatin immunoprecipitation analysis. The combination of SOX2 and ZIC2 TFs activated the enhancer in both the NT and NC. These results indicate that SOX2 and ZIC2, which have been known to play major regulatory roles in neural progenitors, do functionally cooperate. In addition, the recently demonstrated SOX2 expression during the NC development is accounted for at least partly by the D1 enhancer activity. Deletion of the D1 enhancer sequence from the mouse genome, however, did not affect the mouse development, indicating functional redundancies of other enhancers.

Effect of organic matter on estuarine flocculation: a laboratory study using montmorillonite, humic acid, xanthan gum, guar gum and natural estuarine flocs.

BACKGROUND: Riverine particles undergo a rapid transformation when they reach estuaries. The rapid succession of hydrodynamic and biogeochemical regimes forces the particles to flocculate, settle and enter the sediment pool. The rates and magnitudes of flocculation depend on the nature of the particles which are primarily affected by the types and quantities of organic matter (OM). Meanwhile, the OM characteristics vary widely between environments, as well as within a single environment due to seasonal climate and land use variability. We investigated the effect of the OM types and quantities through laboratory experiments using natural estuarine particles from the Mississippi Sound and Atchafalaya Bay as well as model mixtures of montmorillonite and organic molecules (i.e., biopolymers (guar/xanthan gums) and humic acid). RESULTS: Biopolymers promote flocculation but the magnitude depends on the types and quantities. Nonionic guar gum yields much larger flocs than anionic xanthan gum, while both of them exhibit a nonlinear behavior in which the flocculation is the most pronounced at the intermediate OM loading. Moreover, the effect of guar gum is independent of salinity whereas the effect of xanthan gum is pronounced at higher salinity. Meanwhile, humic acid does not affect flocculation at all salinity values tested in this study. These results are echoed in the laboratory manipulation of the natural estuarine particles. Flocculation of the humic acid-rich Mississippi Sound particles is unaffected by the OM, whereas that of biopolymer-rich Atchafalaya Bay particles is enhanced by the OM. CONCLUSIONS: Flocculation is positively influenced by the presence of biopolymers that are produced as the result of marine primary production. Meanwhile, humic acid, which is abundant in the rivers that drain the agricultural soils of Southeastern United States, has little influence on flocculation. Thus, it is expected that humic acid-poor riverine particles (e.g., Mississippi River, and Atchafalaya River, to a lesser degree) may be prone to rapid flocculation and settling in the immediate vicinity of the river mouths when mixed with biopolymer-rich coastal waters. It is also expected that humic acid-rich riverine particles (e.g., Pearl River) may resist immediate flocculation and be transported further away from the river mouth.

The surface properties of Shewanella putrefaciens 200 and S. oneidensis MR-1: the effect of pH and terminal electron acceptors.

BACKGROUND: We investigated the surface characteristics of two strains of Shewanella sp., S. oneidensis MR-1 and S. putrefaciens 200, that were grown under aerobic conditions as well as under anaerobic conditions with trimethylamine oxide (TMAO) as the electron acceptor. The investigation focused on the experimental determination of electrophoretic mobility (EPM) under a range of pH and ionic strength, as well as by subsequent modeling in which Shewanella cells were considered to be soft particles with water- and ion-permeable outermost layers. RESULTS: The soft layer of p200 is significantly more highly charged (i.e., more negative) than that of MR-1. The effect of electron acceptor on the soft particle characteristics of Shewanella sp. is complex. The fixed charge density, which is a measure of the deionized and deprotonated functional groups in the soft layer polymers, is slightly greater (i.e., more negative) for aerobically grown p200 than for p200 grown with TMAO. On the other hand, the fixed charge density of aerobically grown MR1 is slightly less than that of p200 grown with TMAO. The effect of pH on the soft particle characteristics is also complex, and does not exhibit a clear pH-dependent trend. CONCLUSIONS: The Shewanella surface characteristics were attributed to the nature of the outermost soft layer, the extracellular polymeric substances (EPS) in case of p200 and lypopolysaccharides (LPS) in case of MR1 which generally lacks EPS. The growth conditions (i.e., aerobic vs. anaerobic TMAO) have an influence on the soft layer characteristics of Shewanella sp. cells. Meanwhile, the clear pH dependency of the mechanical and morphological characteristics of EPS and LPS layers, observed in previous studies through atomic force microscopy, adhesion tests and spectroscopies, cannot be corroborated by the electrohydrodynamics-based soft particle characteristics which does not exhibited a clear pH dependency in this study. While the electrohydrodynamics-based soft-particle model is a useful tool in understanding bacteria's surface properties, it needs to be supplemented with other characterization methods and models (e.g., chemical and micromechanical) in order to comprehensively address all of the surface-related characteristics important in environmental and other aqueous processes.

Methylglyoxal activates the human transient receptor potential ankyrin 1 channel.

Methylglyoxal (MG) is an endogenous carbonyl compound that is produced in large quantity under hyperglycemic conditions, which are believed to contribute to the development of diabetic neuropathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear. In the present study, we investigated the effect of MG on transient receptor potential ankyrin 1 (TRPA1) activation in human TRPA1-expressing HEK293 cells. MG activated TRPA1-expressing HEK293 cells, but failed to activate human capsaicin-sensitive transient receptor potential vanilloid 1 (TRPV1)-expressing HEK293 cells or mock-transfected HEK293 cells. MG also induced calcium (Ca(2+)) influx in a concentration-dependent manner, and the concentration-response curve indicates that the effect of MG has an EC(50) of 343.1 ± 17.3 µM. Interestingly, the time course in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in human TRPA1-expressing HEK293 showed considerable differences in response to MG and cinnamaldehyde. Furthermore, we examined four endogenous carbonyl compounds, including MG, glyceraldehyde, glycolaldehyde, and glyoxal; only MG notably activated TRPA1-expressing HEK293 cells. These results may provide insight into the TRPA1-mediated effects of MG on diabetic neuropathy.

Endocrine disrupting chemicals in New Orleans surface waters and Mississippi Sound sediments.

Endocrine disrupting compounds (EDCs), represented by steroid hormones, organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and bisphenol A have been determined in four sediment cores from the Gulf of Mexico, from New Orleans surface water (Lake Pontchartrain and Mississippi River), and from the influent and effluent of a New Orleans municipal sewage treatment plant. During the five-month monitoring of selected EDCs in the Mississippi River (MR) and Lake Pontchartrain (LP) in 2008, 21 of 29 OCPs in MR and 17 of 29 OCPs in LP were detected; bisphenol A was detected in all of the samples. Steroid hormones (estrone, 17ß-estradiol and 17α-ethinylestradiol) were detected occasionally. Total EDC (OCPs + PCBs + steroid hormones + bisphenol A) concentrations in the two surface water samples were found to vary from 148 to 1112 ng L(-1). Strong correlation of the distribution of total OCPs, total PCBs and total EDCs between solid and water phases was found in LP, while moderate or no correlation existed in MR. OCPs, PCBs, steroid hormones, and bisphenol A were all detected in the ocean sediments, and total EDCs were measured in the range of 77 to 1796 ng g(-1) dry sediment weight. The EDCs were also found in untreated and treated municipal sewage samples with a removal efficiency of 83% for OCPs but no removal efficiency for 17α-ethinylestradiol.

Effectiveness of diet versus exercise intervention on weight reduction in local Japanese residents.

OBJECTIVE: To evaluate the effect of diet versus exercise intervention on weight reduction. METHODS: Participants were randomly divided by gender, age, and living area into four groups: group DE (diet and exercise, n = 16), group D (diet only, n = 15), group E (exercise only, n = 15), and group C (control, n = 16). This study ultimately aimed to help participants reduce their body mass index (BMI) by 7% of baseline value. Subjects were 62 residents (men and women ranging in age from 40 to 69 years) of two residential areas in Nara Prefecture, Japan, who participated in annual health checkups in 2006. BMI of the participants was ≥24 and <28 kg/m² at baseline examination. All participants agreed to undergo a 6-month intervention between January 2007 and September 2007. RESULTS: In our intention-to-treat analysis, mean change in BMI from baseline to final examination was as follows: group DE mean BMI decreased 6.6%, group D mean BMI decreased 5.3%, group E mean BMI decreased 2.3%, and group C mean BMI decreased 2.2%. The reduction in BMI from baseline to final examination was significant in all groups (DE, p < 0.001; D, p < 0.001; E, p = 0.009; C, p = 0.019). Further, mean abdominal circumference was significantly reduced in all groups. Blood glucose levels were significantly reduced only in group DE (p = 0.047). CONCLUSION: Combined intervention with diet and exercise proved to be effective in weight reduction, whereas exercise intervention alone was not found to be effective.

Deletion of the Hoc and Soc capsid proteins affects the surface and cellular uptake properties of bacteriophage T4 derived nanoparticles.

Recently the use of engineered viral scaffolds in biotechnology and medical applications has been increasing dramatically. T4 phage capsid derived nanoparticles (NPs) have potential advantages as sensors and in biotechnology. These applications require that the physical properties and cellular uptake of these NPs be understood. In this study we used a T4 deletion mutant to investigate the effects of removing both the Hoc and Soc proteins from the capsid surface on T4 tailless NPs. The surface charge, zeta potential, size, and cellular uptake efficiencies for both the T4 NP and T4ΔHocΔSoc NP mutant were measured and compared using dynamic light scattering and flow cytometry and significant differences were detected.

The combined impact of blood pressure category and glucose abnormality on the incidence of cardiovascular diseases in a Japanese urban cohort: the Suita Study.

Few prospective studies have examined the combined impact of blood pressure (BP) categories and glucose abnormalities on the incidence of cardiovascular disease (CVD) in the general Asian population. This study aimed to examine the effect of the combined risks of these factors on the incidence of CVD in a general Japanese population. We studied 5321 Japanese individuals (aged 30-79 years), without CVD at baseline, who received follow-up for an average of 11.7 years. Serum fasting glucose categories were defined according to the 2003 American Diabetes Association recommendations. BP categories were defined by the 2009 Japanese Society of Hypertension Guidelines for the Management of Hypertension. The Cox proportional hazard ratios (HRs) for CVD according to the serum glucose and BP categories were calculated. In 62,036 person-years of follow-up, we documented 364 CVD events (198 stroke and 166 coronary heart disease (CHD)). Compared with normoglycemic subjects, the multivariable HRs (95% confidence intervals (CIs)) for CVD, CHD and stroke were 1.25 (1.00-1.58), 1.46 (1.04-2.04) and 1.11 (0.81-1.52), respectively, in individuals with impaired fasting glucose (IFG), whereas these values were 2.13 (1.50-3.03), 2.28 (1.34-3.88) and 2.08 (1.29-3.35), respectively, in individuals with diabetes mellitus (DM). Compared with normoglycemic and optimal blood pressure (BP) subjects, increased risks of CVD were observed in the normoglycemic subjects with high-normal BP or hypertension, the IFG subjects with normal or higher BP, and the DM subjects regardless of BP category (P-value for interaction=0.046). In conclusion, the high-normal BP subjects in all glucose categories and the normal BP subjects with IFG showed increased risk of CVD in this Japanese population. Further investigation of larger cohorts of DM subjects should be conducted to better understand this phenomenon.

Activation of the human transient receptor potential vanilloid subtype 1 by essential oils.

Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel activated by capsaicin. TRPV1 is expressed not only on human sensory neurons but also on human epidermal and hair follicle keratinocytes. Therefore, TRPV1 could have the potential to be a therapeutic target for skin disorders. To search for novel TRPV1 agonists, we screened 31 essential oils by using human TRPV1-expressing HEK293 cells. TRPV1 was activated by 4 essential oils: rose, thyme geraniol, palmarosa, and tolu balsam. The dose-response curves for TRPV1 activation by the essential oils revealed a rank order potency [the half-maximal effective concentration (EC(50))] of rose>palmarosa>thyme geraniol>tolu balsam, and rank order efficiency (% activity in response to 1 microM capsaicin) of tolu balsam>rose>palmarosa>thyme geraniol. Moreover, the dose-response curves for TRPV1 activation by citronellol (main constituent of rose oil) and geraniol (main constituent of thyme geraniol and palmarosa oils) were consistent with the potency and efficiency of each essential oil. In contrast, benzyl cinnamate and benzyl benzoate (main constituent of tolu balsam oil) and geranyl acetate (main constituent of thyme geraniol oil) did not show TRPV1 activity. In this first-of-its-kind study, we successfully investigated the role of some essential oils in promoting human TRPV1 activation, and also identified two monoterpenes, citronellol and geraniol, as new human TRPV1 agonists.

The relationship between waist circumference and the risk of stroke and myocardial infarction in a Japanese urban cohort: the Suita study.

BACKGROUND AND PURPOSE: Body mass index is most commonly used as the obesity index. Recently, waist circumference (WC) has been shown to be associated with the risk of cardiovascular disease (CVD). However, no studies have observed an association between WC and CVD in Japan. We examined the relationships of WC and body mass index with CVD in a Japanese urban population. METHODS: We studied 5474 Japanese individuals (aged 30 to 79 years without CVD at baseline) who completed a baseline survey and received follow-up through December 2005. WC was measured at the umbilical level of participants in the standing position to the nearest 1 cm. The Cox proportional hazard ratios for CVD according to the quartiles of WC were calculated after adjustment for age, smoking, and drinking status. RESULTS: During a mean follow-up of 11.7 years, 207 strokes and 133 myocardial infarctions were documented. In women, compared with the lowest quartile (WC <70 cm), the hazard ratio (95% CIs) after adjusting for age, smoking, and drinking in the highest quartile (WC >or=84 cm) were 1.85 (1.03 to 3.31) for CVD and 2.64 (1.16 to 6.03) for stroke. However, no such relationships of WC with CVD or stroke risk were observed in men. After further adjustment of hypertension, diabetes, and hypercholesterolemia, all of the mentioned relationships were not statistically significant. No associations of body mass index with CVD or strokes were observed. CONCLUSIONS: WC may be a better predictor for CVD or stroke in Japanese women.

[Volatile organic compounds (VOCs) emitted from furniture and electrical appliances].

Organic chemicals are widely used as ingredients in household products. Therefore, furniture and other household products as well as building products may influence the indoor air quality. This study was performed to estimate quantitatively influence of household products on indoor air quality. Volatile organic compound (VOC) emissions were investigated for 10 products including furniture (chest, desk, dining table, sofa, cupboard) and electrical appliances (refrigerator, electric heater, desktop personal computer, liquid crystal display television and audio) by the large chamber test method (JIS A 1912) under the standard conditions of 28 degrees C, 50% relative humidity and 0.5 times/h ventilation. Emission rate of total VOC (TVOC) from the sofa showed the highest; over 7900 microg toluene-equivalent/unit/h. Relatively high TVOC emissions were observed also from desk and chest. Based on the emission rates, the impacts on the indoor TVOC were estimated by the simple model with a volume of 17.4 m3 and ventilation frequency of 0.5 times/h. The estimated TVOC increment for the sofa was 911 microg/m3, accounting for almost 230% of the provisional target value, 400 microg/m3. The values of estimated increment of toluene emitted from cupboard and styrene emitted from refrigerator were 10% and 16% of guideline values, respectively. These results revealed that VOC emissions from household products may influence significantly indoor air quality.

Aggregation of montmorillonite and organic matter in aqueous media containing artificial seawater.

BACKGROUND: The dispersion-aggregation behaviors of suspended colloids in rivers and estuaries are affected by the compositions of suspended materials (i.e., clay minerals vs. organic macromolecules) and salinity. Laboratory experiments were conducted to investigate the dispersion and aggregation mechanisms of suspended particles under simulated river and estuarine conditions. The average hydrodynamic diameters of suspended particles (representing degree of aggregation) and zeta potential (representing the electrokinetic properties of suspended colloids and aggregates) were determined for systems containing suspended montmorillonite, humic acid, and/or chitin at the circumneutral pH over a range of salinity (0 - 7.2 psu). RESULTS: The montmorillonite-only system increased the degree of aggregation with salinity increase, as would be expected for suspended colloids whose dispersion-aggregation behavior is largely controlled by the surface electrostatic properties and van der Waals forces. When montmorillonite is combined with humic acid or chitin, the aggregation of montmorillonite was effectively inhibited. The surface interaction energy model calculations reveal that the steric repulsion, rather than the increase in electronegativity, is the primary cause for the inhibition of aggregation by the addition of humic acid or chitin. CONCLUSION: These results help explain the range of dispersion-aggregation behaviors observed in natural river and estuarine systems. It is postulated that the composition of suspended particles, specifically the availability of steric polymers such as those contained in humic acid, determine whether the river suspension is rapidly aggregated and settled or remains dispersed in suspension when it encounters increasingly saline environments of estuaries and oceans.

[The impact of sedentary lifestyle on risk factors for cardiovascular disease among Japanese young women].

OBJECTIVE: The purpose of this study was to examine body composition, blood biochemical markers, and dietary intake in 2 groups of young women engaged in different physical activities and to assess the impact of sedentary lifestyle on risk factors for diabetes and cardiovascular disease. METHODS: The subjects were 208 students of a women's university. Of these, 108 majored in nutrition (physically sedentary group, SG) and 100 majored in sports (physically active group, AG). We conducted a survey from mid-June to mid-July in 2004, during which physical examinations, including measurements of body weight and height, evaluation of body composition using dual energy X-ray absorptiometry (DXA), determination of the ankle brachial index (ABI) by measuring the brachial and ankle systolic and assessment of diastolic blood pressure, blood biochemical tests, and examination of 7-day weighted diet records (DRs) were all conducted. The physical and blood biochemical values and the food and nutrient intakes calculated from the DRs were then compared between the groups. RESULTS: We analyzed a total 133 subjects who had completed all the DRs (78 SG subjects and 55 AG subjects). A comparison between the 2 groups revealed mean body mass indices (BMIs) of 20.5 and 21.4 kg/m2 and mean body fat percentages of 29.4% and 22.6% in the SG and AG subjects, respectively. Even though the SG subjects had lower BMIs, they had significantly higher body fat percentages. The ankle systolic blood pressure and ABI were significantly higher in the AG subjects. With regard to blood biochemistry, the HOMA-beta, leptin, and apoprotein-B levels were significantly higher in the SG subjects. The mean energy intakes (kcal/day) of the SG and AG subjects was 1550 and 1853, respectively. The intakes of most nutrients were significantly higher in the AG subjects, and the amount of food consumed by the SG subjects was low. CONCLUSION: The levels of blood biochemical markers such as leptin and apoprotein-B were higher and the ABI was lower in the SG subjects than in the AG subjects. We think that these results are attributable to the accumulation of body fat, including visceral fat. Therefore, it is important for SG subjects to increase their energy expenditure by regular exercise and consume a diet that corresponds to their dietary requirements.

Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation.

Heparan sulphate proteoglycans (HSPGs) have multiple functions relevant to the control of the CNS injury response, particularly in modulating the effects of growth factors and localizing molecules that affect axon growth. We examined the pattern of expression and glycanation of HSPGs in the normal and damaged CNS, and in astrocytes and oligodendrocyte precursors because of their participation in the injury reaction. The composition of HS glycosaminoglycan (GAG) chains was analysed by biochemical analysis and by the binding of antibodies that recognize sulphated epitopes. We also measured levels of HS sulphotransferases and syndecans. Compared with oligodendrocytes, oligodendrocyte precursors have more 2-O-sulphation in their HS GAG. This is accompanied by higher expression of the enzyme responsible for 2-O-sulphation, HS 2-O-sulphotransferase (HS2ST) and a fall in syndecan-1. Astrocytes treated with tumour growth factor (TGF)alpha or TGFbeta to mimic the injury response showed upregulation of syndecan-1 and HS2ST correlating with an increase in 2-O-sulphate residues in their HS GAGs. This also correlated with increased staining with AO4B08 anti-GAG antibody that recognizes high sulphation, and reduced staining with RB4EA12 recognizing low sulphation. After injury to the adult rat brain there was an overall increase in the quantity of HSPG around the injury site, mRNA for HS2ST was increased, and the changes in staining with sulphation-specific antibodies were consistent with an increase in 2-O-sulphated HS. Syndecan-1 was upregulated in astrocytes. The major injury-related change, seen in injured brain and cultured glia, was an increase in 2-O-sulphated HS and increased syndecan-1, suggesting novel approaches to modulating scar formation.

Expression of multiple chondroitin/dermatan sulfotransferases in the neurogenic regions of the embryonic and adult central nervous system implies that complex chondroitin sulfates have a role in neural stem cell maintenance.

Chondroitin/dermatan sulfotransferases (C/D-STs) underlie the synthesis of diverse sulfated structures in chondroitin/dermatan sulfate (CS/DS) chains. Recent reports have suggested that particular sulfated structures on CS/DS polymers are involved in the regulation of neural stem cell proliferation. Here, we examined the gene expression profile of C/D-STs in the neurogenic regions of embryonic and adult mouse central nervous system. Using reverse transcription-polymerase chain reaction analysis, all presently known C/D-STs were detected in the dorsal and ventral telencephalon of the embryonic day 13 (E13) mouse embryo, with the exception of chondroitin 4-O-sulfotransferase (C4ST)-3. In situ hybridization for C4ST-1, dermatan 4-O-sulfotransferase-1, chondroitin 6-O-sulfotransferase (C6ST)-1 and -2, and uronosyl 2-O-sulfotransferase revealed a cellular expression of these sulfotransferase genes in the embryonic germinal zones of the forebrain. The expression of multiple C/D-STs is maintained on cells residing in the adult neural stem cell niche. Neural stem cells cultured as neurospheres maintained the expression of these enzymes. Consistent with the gene expression pattern of C/D-STs, disaccharide analysis revealed that neurospheres and E13 mouse brain cells synthesized CS/DS chains containing monosulfated, but also significant amounts of disulfated, disaccharide units. Functionally, the inhibition of sulfation with sodium chlorate resulted in a significant, dose-dependent decrease in neurosphere number that could not be rescued by the addition of individual purified glycosaminoglycan (GAG) chains, including heparin. These findings argue against a simple charge-based mechanism of GAG chains in neural stem cell maintenance. The synergistic activities of C/D-STs might allow for the adaptive modification of CS/DS proteoglycans with diversely sulfated CS/DS chains in the extracellular microenvironment that surrounds neural stem cells.

Reduction in estimated vitamin A intake induced by new food composition tables in Japan, where vitamin A is taken mostly from plant foods.

A revised edition of the standard tables of food composition was implemented in Japan in 2005; one of the major revision points is the change of retinol activity equivalents for pro-vitamin A carotenoids. This preliminary analysis was conducted to examine whether the revision affects the estimation of vitamin A intake; and if so, to what extent. Accordingly, a field survey was conducted to collect 24-h duplicates of daily foods of citizens, and 26 adult women volunteered. Application of the procedures in the new and previous standard tables of food composition gave 537 microg retinol activity equivalent and 704 microg retinol equivalence, respectively, for daily vitamin A intake. Thus, the changes in retinol activity equivalents induced substantial reduction (by 24%) in estimation of vitamin A intake among the Japanese population, for whom pro-vitamin A carotenoids in plant foods are the major sources (76%) for vitamin A, and retinol accounts for only 35% (on the retinol activity equivalent basis).

Limited acceptance of globalization in food habits among middle-aged women in Osaka, Japan.

The study was initiated to identify the effects of recent changes in dietary pattern in Japan on nutrient intake. In the large city of Osaka, Japan, 24-h food duplicate samples were collected from 26 middle-aged women, and nutrients in the duplicates were estimated in reference to standard tables of food composition. The subjects took 1844 kcal (7.72 MJ) energy, 67.5 g protein, and 54.5 g lipid (37% from plants) per day. Micro-nutrient intakes were generally sufficient, but NaCl intake tended to be excessive, and the relatively high body mass index (>25 in six cases) suggested a possibility of over-eating. The food composition was rich in rice and fish, being basically of a traditional type. Consumption of bread, an acquired habit, was observed in 65% of the breakfasts but less so in lunch and none in dinner. Thus, the acceptance of bread in place of rice was limited and did not induce substantial alteration in nutrient intakes.

Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia.

Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the CNS after injury and inhibit axon regeneration mainly through their glycosaminoglycan (CS-GAG) chains. We have analysed the mRNA levels of the CS-GAG synthesizing enzymes and measured the CS-GAG disaccharide composition by chromatography and immunocytochemistry. Chondroitin 6-sulfotransferase 1 (C6ST1) is up-regulated in most glial types around cortical injuries, and its sulphated product CS-C is also selectively up-regulated. Treatment with TGFalpha and TGFbeta, which are released after brain injury, promotes the expression of C6ST1 and the synthesis of 6-sulphated CS-GAGs in primary astrocytes. Oligodendrocytes, oligodendrocyte precursors and meningeal cells are all inhibitory to axon regeneration, and all express high levels of CS-GAG, including high levels of 6-sulphated GAG. In axon growth-inhibitory Neu7 astrocytes C6ST1 and 6-sulphated GAGs are expressed at high levels, whereas in permissive A7 astrocytes they are not detectable. These results suggest that the up-regulation of CSPG after CNS injury is associated with a specific sulphation pattern on CS-GAGs, mediating the inhibitory properties of proteoglycans on axonal regeneration.