Jung, Ga-Young;Won, Sae-Bom;Kim, Juhae;Jeon, Sookyoung;Han, Anna;Kwon, Young Hye
Toxicological Research
/
v.29
no.1
/
pp.7-14
/
2013
Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.
Park, Eunju;Baek, Aran;Kim, Mijeong;Lee, Seon Woo;Lee, Eunji;Choi, Mi-Joo;Lee, Jeehyun;Song, Yeong Ok
Journal of the Korean Society of Food Science and Nutrition
/
v.43
no.11
/
pp.1627-1634
/
2014
The recipe for sujeonggwa, a Korean traditional sweet drink containing cinnamon, ginger, sugar, or honey, was modified by replacing sugar with alternative sweeteners [stevia or short-chain frutooligosaccharide (scFOS)] in order to improve the health functionality of sujeonggwa. The aim of this study was to evaluate the effects of modified sujeonggwa on lipid peroxidation and oxidized DNA damage in diet-induced hypercholesterolemic ApoE knockout mice. Hypercholesterolemia was induced in 6-week-old male mice by administration of a high cholesterol diet (1.25% cholesterol, 0.5% cholic acid, and 10% coconut oil) for 4 weeks, after which mice were divided into five groups: sucrose solution-fed control group, sujeonggwa containing sucrose group, sucrose+stevia group, sucrose+stevia+scFOS group, and commercially available sujeonggwa group as a positive control. After 6 weeks, sujeonggwa supplementation resulted in reduced hepatic thiobarbituric acid reactive substances (TBARS), regardless of sweetener type. However, reduction of hepatic TBARS by commercially available sujeonggwa was insignificant. Both endogenous and $H_2O_2$-induced DNA damage in hepatocytes and splenocytes were significantly reduced only in the sujeonggwa containing stevia group compared to the sucrose-fed control group. There were no significant effects of sujeonggwa supplementation on total radical trapping potential, lipid peroxidation, or DNA damage in blood. These results suggest that sujeonggwa has protective effects against hepatic lipid peroxidation and DNA damage in hepatocytes or splenocytes from diet-induced hypercholesterolemic ApoE knockout mice, and the type of sweetener should be modified to improve the health benefits of sujeonggwa.
This study was undertaken to examine the influence of soluble non-starch polysaccharides on growth performance, mucin secretion, and endogenous amino acid flows in weaner pigs. Different levels (0, 4 and 7.5%) of purified corn arabinoxylan (AX) or barley $\beta$-glucan extract (BG) were substituted for cellulose in a purified diet based on starch, sucrose and enzymatically hydrolyzed casein. All diets contained titanium oxide as an indigestible marker. Each experimental diet was fed to five, 6-wk old weaner pigs for 21 days. Average daily gain (p<0.05) and feed conversion ratio (p<0.01) were improved with dietary inclusion of 7.5% AX and BG, indicating high degradation rates of AX and BG in pigs. Crude mucin contents and endogenous nitrogen flow were increased (p<0.05) with increased levels of AX, but not with BG. Numerical increases in endogenous amino acid flow (EAAF) were observed with increased levels of AX but no definite trend with BG. Endogenous amino acid flow in pigs fed mixed NSP diets (4% BG and 3.5% cellulose) was significantly higher (p<0.05) than those fed 7.5% BG diets. Among diets containing pure sources of soluble non-starch polysaccharides, endogenous amino acid flows were highest in 7.5% AX (p<0.05), intermediate in BG, and lowest in control diet. Increased flows (p<0.01) of threonine, proline and serine in pigs fed 7.5% AX diets are consistent with the increased flow of crude mucin determined in this treatment. In conclusion, mucin and endogenous amino acid flows were increased with dietary inclusion of AX, which could be related to its physicochemical property, particularly its high water-holding capacity. In contrast, $\beta$-glucan, due to its high degradation rate in pig, may be considered as unimportant factor in inducing mucin and endogenous amino acid secretions, at least at levels such as those used in this study.
Park, Jong-Seol;Lee, Byung-Cheol;Doo, Ho-Kyung;Ahn, Young-Min;Ahn, Se-Young
The Journal of Internal Korean Medicine
/
v.30
no.2
/
pp.257-269
/
2009
Objective : Obesity is an important cause of diabetes, and lipotoxicity causes insulin resistance. Recently a lot of research is being done on PPAR-${\alpha}$. TNF-${\alpha}$. adiponectin, and leptin, which are important obesity related factors. In this study, we investigated the effects of Supungsunki-hwan on high fat. high carbohydrate diet-induced obese type 2 diabetic mouse models. Methods: Diabetes was induced in ICR male mouse (30${\pm}$5g) with Surwit's high fat, high sucrose diet. Mice were divided into 4 groups(n=10) of Normal. Control. Supungsunkj-hwan group. and acarbose group. The Supungsunki-hwsn group was given 10% Supungsunkj-hwan in their diet. and the acarbose group was given 0.5% acarbose in their diet. After 6 weeks. body weight. food intake, FBS and OGTT. lipid profile and liver enzymes, epididymal fat weight, and gene expression of leptin, adiponectin, TNF-${\alpha}$ and PPAR-${\alpha}$ were measured. Leptin. adiponectin. tumor necrosis factor(TNF)-${\alpha}$ and peroxisome proliferator-activated receptor (PPAR)-${\alpha}$ were evaluated by reverse transcription-polymerase chain reaction. Results : Supungsunkj-hwan increased the gene expression of PPAR-${\alpha}$, which reduces lipotoxicity and insulin resistance. Supungsunkj-hwan also significantly reduced triglyceride. AST. ALT serum levels. and 1 hour oral glucose tolerance levels. Conclusion : These results show that Supungsunkj-hwan improves insulin resistance in the liver and muscles, by reducing triglyceride levels and lipotoxicity through increased PPAR-${\alpha}$ gene expression. This is supported by the fact that Supungsunkj-hwan significantly reduces 1 hour oral glucose tolerance levels. Therefore we suggest that Supungsunkj-hwan would be an effective treatment for obese type 2 diabetic patients.
Journal of the Korean Society of Food Science and Nutrition
/
v.30
no.5
/
pp.1004-1009
/
2001
Acid hydrolysates of cocoon was gained by acid hydrolysis of 2 N HCl, 11$0^{\circ}C$, 48 hours, neutralization and desalting from the cocoon. The amino acid compositions of acid hydrolysates of cocoon were glycine 43.25%, alanine 34.39%, serine 10.05% and valine 2.44%. The contents of essential amino acid was 10.05%. Food efficiency ratio of acid hydrolysates of cocoon group was equal to the reference protein, casein. Liver weight, GOT, GPT activity, serum albumin and serum total protein level of rats were not significantly different among the experimental groups. Therefore, the protein acid hydrolysates of cocoon is not of high quality. When the rat fed with high cholesterol, high lipid, and high sucrose diet was administered with 5% acid hydrolysates of cocoon, its plasma lipids concentration of acid hydrolysates of cocoon was favorably affected: its triglyceride was decreased, and the level of phospholipid and HDL cholesterol were increased. There was also an unfavorable effect: the levels of LDL cholesterol and total cholesterol went up. Therefore, the acid hydrolysates of cocoon is not a good protein food source, but is can be used a cosmetic, medical, or packing material. Further research will reveal how it will affect or improve plasma lipid.
BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.
Journal of the Korean Applied Science and Technology
/
v.2
no.1
/
pp.57-66
/
1985
The possible effects of 10% carbohydrate containting diets on the serum glucose and lipids values were studied with normal and alloxan - diabetic male rats for a period of 28 days. The diets were supplemented with either glucose, cornstarch or sucrose, fructose or the basal diet containing no added carbohy drates. After this period, 3 to 4 rats among the each group were killed and samples of serum, liver, spleen and kidney were collected. The others were rendered diabetic by the intraperitoneal injection of alloxan ($190mg/\frac{wt}{kg}$). Then original feeding scedule was continued for 3 days in all five diabetic groups, before the collection of tissue samples and serum. Feeding the nondiabetic rats with glucose and fructose delayed the bodyweight development relatively compared with nonsugar group. The weight deductions after alloxan injection were similar in all feeding groups. All diabetic animals exhibited increased blood glucose triglceride levels but almost unchanged total cholesterol values. Blood glucose values for nondiabetic rats were normal ranges, and then glucose feeding group was the highest. Total - cholesterol values were the highest in nondiabetic rats fed glucose, fructose and in diabetics fed sucrose, glucose. Triglyceride values were the highest in nondiabetic rats fed sucrose, and no difference in diabetic rats. Some cornstarch group exhibited fatty-livers in diabetic and nondiabetic, and more studies need.
Kim, Min-Kyung;Choi, Ah-Ri;Han, Gi-Sung;Jeong, -Seok-Geun;Oh, Mi-Hwa;Kim, Dong-Hun;Ham, Jun-Sang
Journal of Dairy Science and Biotechnology
/
v.29
no.1
/
pp.17-22
/
2011
Milk intake is widely recommended for healthy diet, not only for bone growth and maintenance, but also as a protein, calcium and magnesium sources as part of an adequate diet. Many research suggest that milk and dairy products are associated with a lower risk of type 2 diabetes mellitus (T2DM). Milk and dairy products are low Glycemic index (GI) and Glycemic load (GL) foods. The GI and GL are useful tools to choose foods to help control blood glucose levels in people with diabetes. The GI and GL of milk are 32~42 and 4~5, respectively, and which are about 1/2 and 1/5 of boiled rice. The mechanisms underlying the effects of dairy on T2DM development includes the calcium and vitamin D content in dairy foods and the possible positive effect of high milk and calcium intake on weight control. The role of dairy products on reducing the risk of diabetes can be inferred from the reports that lower serum IGF-1 levels were positively associated with diabetes and the girls with low milk intake had significantly lower IGF-1. Accumulating data from both patients and animal models suggest that microbial ecosystems associated with the human body, especially the gut microbiota, may be associated with several important diseases, such as inflammatory bowel disease, obesity, diabetes and cardiovascular disease. It was thought that fermented milk containing lots of probiotics can be useful for controling blood glucose levels and preventing complication of diabetes, but sucrose in commercial yogurt should be substituted. There are some reports of oligosaccharide, xylitol, and stevia as a potentially useful sweetener in the diabetic diet.
Koo, Hyun Jung;Kang, Se Chan;Jang, Seon-A;Kwon, Jung-Eun;Sohn, Eunsoo;Sohn, Eun-Hwa
Korean Journal of Plant Resources
/
v.27
no.4
/
pp.271-278
/
2014
Rubus coreanus has been used as a traditional medicine in Asia because of its various pharmacological properties. This study examined the effects of protocatechuic acid (PCA), one of phenolic compounds derived from R. coreanus on the lipid metabolism in high cholesterol diet-induced mice. A total of 30 male C57BL/6 mice were divided into 5 groups with 6 mice in each group as follows: (1) Control mice received normal diet (ND). (2) Mice received high-cholesterol diet (HCD) plus water, 10% sucrose solution and treated daily oral phosphate-buffered-saline (PBS) of equal volumes through gavage. (3) Mice received HCD and treated daily with 25 mg/kg b.w./day of PCA (4) with 50 mg/kg b.w./day or (5) with 10 mg/kg b.w./day of simvastatin via oral gavage for 12 weeks. Body weights were measured weekly for a period of experiment. After treatment, liver, thymus, spleen and kidney were harvested and weighed, and the lipid metabolite profiles (total cholesterol, triglyceride (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and liver-damaging markers (GOT and GPT) in serum were examined. PCA significantly reduced the total cholesterol, TG, LDL-c level and increased the HDL-c level. PCA administration also significantly reduced the levels of GOT and GPT. These results indicate that the PCA could be used as a functional material for lowering lipid and an adjuvant for the treatment of hyperlipemia.
This study was performed to investigate the effect of mixed glucomannan(G) and wheycalcium(W) on the level of serum cholesterol in rats(Female Sprague-Dawley) fed high cholesterol diet($1.0\%$ : HCD) and also on the level of blood glucose in rats fed high glucose diet ($70\%$ : HGD) for 4 weeks. The results were follows as 1. The level of serum cholesterol were decreased in the rank order HCD>HCDG>HCDGW>ND, 2. HCDG showed a decrese of about $23.84\%$ but HCDGW showed a decrese of about $42.38\%$ compared with the increasing rate of HCD in serum cholesterol, 3. The level of blood glucose were decreased in the rank order HGD>HGDG>HGDGW>ND, 4. HGDG showed a decrese of about $6.63\%$ but HGDGW showed a decrese of about $36.14\%$ compared with the increasing rate of HGD in blood glucose, 5. The mixture of glucomannan and wheycalcium on the serum cholesterol and blood glucose in rats was most effect of all.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.