Browsing by Subject "LIPIDS"

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  • Surakka, Ida; Isaacs, Aaron; Karssen, Lennart C.; Laurila, Pirkka-Pekka P.; Middelberg, Rita P. S.; Tikkanen, Emmi; Ried, Janina S.; Lamina, Claudia; Mangino, Massimo; Igl, Wilmar; Hottenga, Jouke-Jan; Lagou, Vasiliki; van der Harst, Pim; Leach, Irene Mateo; Esko, Tonu; Kutalik, Zoltan; Wainwright, Nicholas W.; Struchalin, Maksim V.; Sarin, Antti-Pekka; Kangas, Antti J.; Viikari, Jorma S.; Perola, Markus; Rantanen, Taina; Petersen, Ann-Kristin; Soininen, Pasi; Johansson, Asa; Soranzo, Nicole; Heath, Andrew C.; Papamarkou, Theodore; Prokopenko, Inga; Toenjes, Anke; Kronenberg, Florian; Doering, Angela; Rivadeneira, Fernando; Montgomery, Grant W.; Whitfield, John B.; Kahonen, Mika; Lehtimaki, Terho; Freimer, Nelson B.; Willemsen, Gonneke; de Geus, Eco J. C.; Palotie, Aarno; Sandhu, Manj S.; Waterworth, Dawn M.; Metspalu, Andres; Stumvoll, Michael; Uitterlinden, Andre G.; Jula, Antti; Navis, Gerjan; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.; Taskinen, Marja-Riitta; Ala-Korpela, Mika; Kaprio, Jaakko; Kyvik, Kirsten O.; Boomsma, Dorret I.; Pedersen, Nancy L.; Gyllensten, Ulf; Wilson, James F.; Rudan, Igor; Campbell, Harry; Pramstaller, Peter P.; Spector, Tim D.; Witteman, Jacqueline C. M.; Eriksson, Johan G.; Salomaa, Veikko; Oostra, Ben A.; Raitakari, Olli T.; Wichmann, H. -Erich; Gieger, Christian; Jaervelin, Marjo-Riitta; Martin, Nicholas G.; Hofman, Albert; McCarthy, Mark I.; Palotie, Leena; van Duijn, Cornelia M.; Aulchenko, Yurii S.; Ripatti, Samuli (2011)
  • Tverin, Malin; Granroth, Janne; Abrahamsson, Alexander; Tang, Patrik Anthony; Pihlström, Henry; Lundström, Karl; Käkelä, Reijo (2021)
    Increased numbers of great cormorants (Phalacrocorax carbo) in the Baltic Sea may have local impacts on fisheries and salmonid hatcheries. We studied spatial and temporal variability in cormorant diet, and potential consumption of hatchery salmonids, by analysing knee subcutaneous adipose tissue fatty acids (FA) of specimens (N = 77) collected along Swedish and Finnish coasts in different seasons during 2013–2017. The FA profiles of the subspecies sinensis and carbo were similar, with large individual variation. The proportion of C18 polyunsaturated FAs (PUFAs) was the largest in the north, whereas the proportion of C20–22 monounsaturated FAs (MUFAs) increased towards the south, reflecting diminishing freshwater and increasing marine food web characteristics towards the south. As an exception, the C20–22 MUFA percentage was high in sinensis collected in June 2017 from the northern Baltic Sea. The source of C20–22 MUFAs was probably hatchery salmonids, raised on ocean fish hatchery feed and released 10 days before, near the cormorant capture site. The FA profiles of northern and southern cormorants differed from each other both in early and late summer samples, suggesting spatially different diets. The largest individual variation was found in 22:1n-11, characteristic of ocean zooplanktivorous fish, and likely originating from Atlantic wild or Baltic Sea hatchery-reared fish. This study shows that adipose tissue FA profiles can be used as proxies for seabird diet monitoring and indicators of predation on hatchery-reared fish. Obtaining quantitative estimates on the proportions of dietary fish species requires future feeding experiments, allowing calibration between the FA compositions and diet.
  • Malkamäki, Aapo Erkki Matias; Sharma, Vivek (2019)
    Mitochondrial cytochrome c oxidase couples the reduction of oxygen to proton pumping. Despite an overall good understanding of its molecular mechanism, the role of cardiolipin in protein function is not understood. Here, we have studied the cardiolipin-protein interactions in a dynamic context by means of atomistic molecular dynamics simulations performed on the entire structure of monomeric and dimeric forms of the enzyme. Several microseconds of simulation data reveal that the crystallographic cardiolipin molecules that glue two monomers together bind weakly in hybrid and single-component lipid bilayers and dissociate rapidly. Atomistic simulations performed in the absence of tightly bound cardiolipin molecules strongly perturb the structural integrity of subunits III and Vila, thereby highlighting an indispensable nature of lipid-protein interactions in enzyme function such as proton uptake and oxygen channeling. Our results demonstrate the strength of molecular simulations in providing direct atomic description of lipid-protein processes that are difficult to achieve experimentally.
  • Miettinen, Helena E.; Rono, Kristiina; Koivusalo, Saila B.; Eriksson, Johan G.; Gylling, Helena (2018)
    Background and aims: Impaired glucose metabolism during pregnancy may associate with changes in fetal cholesterol metabolism. We investigated if gestational diabetes mellitus (GDM) affects newborn cholesterol metabolism as determined by cord blood squalene and non-cholesterol sterols. Furthermore, we examined potential correlations between cord blood and maternal serum non-cholesterol sterols. Methods: Pregnant women at risk for GDM (BMI>30 kg/m(2)) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were taken in the third trimester of pregnancy, and cord blood samples collected from their newborns at birth. Squalene and non-cholesterol sterols were analyzed from serum and cord blood by gas liquid chromatography. All women with GDM were in good glycaemic control. Results: The ratios of squalene and non-cholesterol sterols to cholesterol (100 x mu mol/mmol of cholesterol) in cord blood did not differ between the infants born to mothers with GDM (n = 15) or mothers with normal glucose tolerance (n = 13). The ratios of sitosterol and campesterol to cholesterol in the cord blood correlated with the corresponding maternal serum ratios (r = 0.70, p <0.0001) in both groups. Conclusions: In obese women under good glycaemic control, GDM did not affect newborn cholesterol metabolism. Cord blood sitosterol and campesterol ratios to cholesterol correlated with the corresponding maternal serum ratios thus potentially reflecting maternal-fetal cholesterol transport. (C) 2018 Elsevier B.V. All rights reserved.
  • Keinanen, Marja; Kakela, Reijo; Ritvanen, Tiina; Myllyla, Timo; Ponni, Jukka; Vuorinen, Pekka J. (2017)
    Sprat (Sprattus sprattus) and small herring (Clupea harengus) are the dominant prey fish of Atlantic salmon (Salmo salar) in the Baltic Sea. If the fatty acid (FA) proportions of sprat and herring differ, the dietary history of ascending salmon could be determined from their FA profiles. Therefore, we investigated the FA composition of several age groups of whole sprat and small herring, caught from the three main feeding areas of salmon in autumn and spring. Oleic acid (18: 1n-9) was the most prevalent FA in sprat and characteristic of this species. In herring, palmitic acid (16: 0) was the most common FA, but herring lipid was characterized by n-6 polyunsaturated FAs, and moreover, by palmitoleic acid (16: 1n-7) and vaccenic acid (18: 1n-7). Due to the higher lipid content of sprat, the concentrations of all other FAs, excluding these, were higher in sprat than in herring. The concentration of docosahexaenoic acid (DHA, 22: 6n-3) increased with an increase in the lipid content and was consequently highest in the youngest specimens, being in young sprat almost double that of young herring, and 2.6 times higher in the sprat biomass than in that of herring. As a result of a decrease in the DHA concentration with age, the ratio thiamine/DHA increased with respect to age in both species, and was lower in sprat than in herring. It is concluded that an abundance of DHA in the diet of salmon most likely increases oxidative stress because of the susceptibility of DHA to peroxidation, and thus decreases thiamine resources of fasting, prespawning salmon. Because the FA composition of sprat and herring differs, and the relative abundancies of prey fish differ between the feeding areas of salmon, the feeding area of ascending salmon can most probably be derived by comparing their FA profiles.
  • Lempiäinen, Juha; Ijäs, Petra; Niiranen, Teemu J.; Kaste, Markku; Karhunen, Pekka J.; Lindsberg, Perttu J.; Erkinjuntti, Timo; Melkas, Susanna (2020)
    Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort.
  • Rosa-Sibakov, Natalia; Mäkelä, Noora; Aura, Anna-Marja; Sontag-Strohm, Tuula; Nordlund, Emilia (2020)
    The objective of this work was to evaluate the role of beta-glucan molecular weight (M-w) and the presence of other carbohydrates on the physiological functionality of oat branviaanin vitrodigestion study. A complete approach using three differentin vitrodigestion models (viscosity of the small intestine digest, reduction of bile acids and on-line measurement of gas evolution) was used to predict the physiological functionality of enzymatically modified oat bran concentrate (OBC). OBC was enzymatically treated with two beta-glucanase preparations at three different levels in order to specifically decrease beta-glucanM(w)(Pure: purified beta-glucanase) or beta-glucan and other cell wall polysaccharides (Mix: commercial food-grade cell wall degrading enzyme preparation). TheM(w)of beta-glucan in OBC was tailored to high (1000 kDa), medium (200-500 kDa) and low (
  • Setala, Niko L.; Holopainen, Juha M.; Metso, Jari; Yohannes, Gebrenegus; Hiidenhovi, Jaakko; Andersson, Leif C.; Eriksson, Ove; Robciuc, Alexandra; Jauhiainen, Matti (2010)
  • Palviainen, Mari; Saari, Heikki; Kärkkäinen, Olli; Pekkinen, Jenna; Auriola, Seppo; Yliperttula, Marjo; Puhka, Maija; Hanhineva, Kati; Siljander, Pia R-M (2019)
    One of the greatest bottlenecks in extracellular vesicle (EV) research is the production of sufficient material in a consistent and effective way using in vitro cell models. Although the production of EVs in bioreactors maximizes EV yield in comparison to conventional cell cultures, the impact of their cell growth conditions on EVs has not yet been established. In this study, we grew two prostate cancer cell lines, PC-3 and VCaP, in conventional cell culture dishes and in two-chamber bioreactors to elucidate how the growth environment affects the EV characteristics. Specifically, we wanted to investigate the growth condition-dependent differences by non-targeted metabolite profiling using liquid chromatography-mass spectrometry (LC-MS) analysis. EVs were also characterized by their morphology, size distribution, and EV protein marker expression, and the EV yields were quantified by NTA. The use of bioreactor increased the EV yield >100 times compared to the conventional cell culture system. Regarding morphology, size distribution and surface markers, only minor differences were observed between the bioreactor-derived EVs (BR-EVs) and the EVs obtained from cells grown in conventional cell cultures (C-EVs). In contrast, metabolomic analysis revealed statistically significant differences in both polar and non-polar metabolites when the BR-EVs were compared to the C-EVs. The results show that the growth conditions markedly affected the EV metabolite profiles and that metabolomics was a sensitive tool to study molecular differences of EVs. We conclude that the cell culture conditions of EV production should be standardized and carefully detailed in publications and care should be taken when EVs from different production platforms are compared with each other for systemic effects.
  • Tikkanen, Emmi; Minicocci, Ilenia; Hällfors, Jenni; Di Costanzo, Alessia; D'Erasmo, Laura; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Wurtz, Peter; Jauhiainen, Matti; Olkkonen, Vesa M.; Arca, Marcello (2019)
    Objective- Loss-of-function (LOF) variants in the ANGPTL3 (angiopoietin-like protein 3) have been associated with low levels of plasma lipoproteins and decreased coronary artery disease risk. We aimed to determine detailed metabolic effects of genetically induced ANGPTL3 deficiency in fasting and postprandial state. Approach and Results- We studied individuals carrying S17X LOF mutation in ANGPTL3 (6 homozygous and 32 heterozygous carriers) and 38 noncarriers. Nuclear magnetic resonance metabolomics was used to quantify 225 circulating metabolic measures. We compared metabolic differences between LOF carriers and noncarriers in fasting state and after a high-fat meal. In fasting, ANGPTL3 deficiency was characterized by similar extent of reductions in LDL (low-density lipoprotein) cholesterol (0.74 SD units lower concentration per LOF allele [95% CI, 0.42-1.06]) as observed for many TRL (triglyceride-rich lipoprotein) measures, including VLDL (very-low-density lipoprotein) cholesterol (0.75 [95% CI, 0.45-1.05]). Within most lipoprotein subclasses, absolute levels of cholesterol were decreased more than triglycerides, resulting in the relative proportion of cholesterol being reduced within TRLs and their remnants. Further, beta-hydroxybutyrate was elevated (0.55 [95% CI, 0.21-0.89]). Homozygous ANGPTL3 LOF carriers showed essentially no postprandial increase in TRLs and fatty acids, without evidence for adverse compensatory metabolic effects. Conclusions- In addition to overall triglyceride- and LDL cholesterol-lowering effects, ANGPTL3 deficiency results in reduction of cholesterol proportion within TRLs and their remnants. Further, ANGPTL3 LOF carriers had elevated ketone body production, suggesting enhanced hepatic fatty acid beta-oxidation. The detailed metabolic profile in human knockouts of ANGPTL3 reinforces inactivation of ANGPTL3 as a promising therapeutic target for decreasing cardiovascular risk.
  • Hallamaa, Raija; Batchu, Krishna (2016)
    Background: Lipids have become an important target for searching new biomarkers typical of different autoimmune and allergic diseases. The most common allergic dermatitis of the horse is related to stings of insects and is known as insect bite hypersensitivity (IBH) or summer eczema, referring to its recurrence during the summer months. This intense pruritus has certain similarities with atopic dermatitis of humans. The treatment of IBH is difficult and therefore new strategies for therapy are needed. Autoserum therapy based on the use of serum phospholipids has recently been introduced for horses. So far, serum lipids relating to these allergic disorders have been poorly determined. The main aim of this study was to analyse phospholipid profiles in the sera of horses with allergic dermatitis and in their healthy controls and to further assess whether these lipid profiles change according to the clinical status after therapy. Methods: Sera were collected from 10 horses with allergic dermatitis and from 10 matched healthy controls both before and 4 weeks after the therapy of the affected horses. Eczema horses were treated with an autogenous preparation made from a horse's own serum and used for oral medication. Samples were analysed for their phospholipid content by liquid chromatography coupled to a triple-quadrupole mass spectrometer (LC-MS). Data of phospholipid concentrations between the groups and over the time were analysed by using the Friedman test. Correlations between the change of concentrations and the clinical status were assessed by Spearman's rank correlation test. Results: The major phospholipid classes detected were phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylinositol (PI) and phosphatidylethanolamine (PE). Eczema horses had significantly lower total concentrations of PC (p <0.0001) and SM (p = 0.0115) than their healthy controls. After a 4-week therapy, no significant differences were found between the groups. Changes in SM concentrations correlated significantly with alterations in clinical signs (p = 0.0047). Conclusions: Horses with allergic dermatitis have an altered phospholipid profile in their sera as compared with healthy horses and these profiles seem to change according to their clinical status. Sphingomyelin seems to have an active role in the course of equine insect bite hypersensitivity.
  • Taddei, Cristina; Zhou, Bin; Bixby, Honor; Carrillo-Larco, Rodrigo M.; Danaei, Goodarz; Jackson, Rod T.; Farzadfar, Farshad; Sophiea, Marisa K.; Di Cesare, Mariachiara; Iurilli, Maria Laura Caminia; Martinez, Andrea Rodriguez; Asghari, Golaleh; Dhana, Klodian; Gulayin, Pablo; Kakarmath, Sujay; Santero, Marilina; Voortman, Trudy; Riley, Leanne M.; Cowan, Melanie J.; Savin, Stefan; Bennett, James E.; Stevens, Gretchen A.; Paciorek, Christopher J.; Aekplakorn, Wichai; Cifkova, Renata; Giampaoli, Simona; Kengne, Andre Pascal; Khang, Young-Ho; Kuulasmaa, Kari; Laxmaiah, Avula; Margozzini, Paula; Mathur, Prashant; Nordestgaard, Borge G.; Zhao, Dong; Aadahl, Mette; Abarca-Gomez, Leandra; Rahim, Hanan Abdul; Abu-Rmeileh, Niveen M.; Acosta-Cazares, Benjamin; Adams, Robert J.; Agdeppa, Imelda A.; Aghazadeh-Attari, Javad; Aguilar-Salinas, Carlos A.; Agyemang, Charles; Ahluwalia, Tarunveer S.; Ahmad, Noor Ani; Ahmadi, Ali; Ahmadi, Naser; Ahmed, Soheir H.; Ahrens, Wolfgang; Ajlouni, Kamel; Alarouj, Monira; AlBuhairan, Fadia; AlDhukair, Shahla; Ali, Mohamed M.; Alkandari, Abdullah; Alkerwi, Ala'a; Aly, Eman; Amarapurkar, Deepak N.; Amouyel, Philippe; Andersen, Lars Bo; Anderssen, Sigmund A.; Anjana, Ranjit Mohan; Ansari-Moghaddam, Alireza; Aounallah-Skhiri, Hajer; Araujo, Joana; Ariansen, Inger; Aris, Tahir; Arku, Raphael E.; Arlappa, Nimmathota; Aryal, Krishna K.; Aspelund, Thor; Assuncao, Maria Cecilia F.; Auvinen, Juha; Avdicova, Maria; Azevedo, Ana; Azizi, Fereidoun; Azmin, Mehrdad; Balakrishna, Nagalla; Bamoshmoosh, Mohamed; Banach, Maciej; Bandosz, Piotr; Banegas, Jose R.; Barbagallo, Carlo M.; Barcelo, Alberto; Barkat, Amina; Bata, Iqbal; Batieha, Anwar M.; Batyrbek, Assembekov; Baur, Louise A.; Beaglehole, Robert; Belavendra, Antonisamy; Ben Romdhane, Habiba; Benet, Mikhail; Benn, Marianne; Berkinbayev, Salim; Bernabe-Ortiz, Antonio; Bernotiene, Gailute; Bettiol, Heloisa; Bhargava, Santosh K.; Bi, Yufang; Bienek, Asako; Bikbov, Mukharram; Bista, Bihungum; Bjerregaard, Peter; Bjertness, Espen; Bjertness, Marius B.; Bjorkelund, Cecilia; Bloch, Katia; Blokstra, Anneke; Bo, Simona; Boehm, Bernhard O.; Boggia, Jose G.; Boissonnet, Carlos P.; Bonaccio, Marialaura; Bongard, Vanina; Borchini, Rossana; Borghs, Herman; Bovet, Pascal; Brajkovich, Imperia; Breckenkamp, Juergen; Brenner, Hermann; Brewster, Lizzy M.; Bruno, Graziella; Bugge, Anna; Busch, Markus A.; de Leon, Antonio Cabrera; Cacciottolo, Joseph; Can, Gunay; Candido, Ana Paula C.; Capanzana, Mario; Capuano, Eduardo; Capuano, Vincenzo; Cardoso, Viviane C.; Carvalho, Joana; Casanueva, Felipe F.; Censi, Laura; Chadjigeorgiou, Charalambos A.; Chamukuttan, Snehalatha; Chaturvedi, Nish; Chen, Chien-Jen; Chen, Fangfang; Chen, Shuohua; Cheng, Ching-Yu; Cheraghian, Bahman; Chetrit, Angela; Chiou, Shu-Ti; Chirlaque, Maria-Dolores; Cho, Belong; Cho, Yumi; Chudek, Jerzy; Claessens, Frank; Clarke, Janine; Clays, Els; Concin, Hans; Confortin, Susana C.; Cooper, Cyrus; Costanzo, Simona; Cottel, Dominique; Cowell, Chris; Crujeiras, Ana B.; Csilla, Semanova; Cui, Liufu; Cureau, Felipe; D'Arrigo, Graziella; d'Orsi, Eleonora; Dallongeville, Jean; Damasceno, Albertino; Dankner, Rachel; Dantoft, Thomas M.; Dauchet, Luc; Davletov, Kairat; De Backer, Guy; De Bacquer, Dirk; de Gaetano, Giovanni; De Henauw, Stefaan; de Oliveira, Paula Duarte; De Ridder, David; De Smedt, Delphine; Deepa, Mohan; Deev, Alexander D.; Dehghan, Abbas; Delisle, Helene; Dennison, Elaine; Deschamps, Valerie; Dhimal, Meghnath; Di Castelnuovo, Augusto F.; Dika, Zivka; Djalalinia, Shirin; Dobson, Annette J.; Donfrancesco, Chiara; Donoso, Silvana P.; Doring, Angela; Dorobantu, Maria; Dragano, Nico; Drygas, Wojciech; Du, Yong; Duante, Charmaine A.; Duda, Rosemary B.; Dzerve, Vilnis; Dziankowska-Zaborszczyk, Elzbieta; Eddie, Ricky; Eftekhar, Ebrahim; Eggertsen, Robert; Eghtesad, Sareh; Eiben, Gabriele; Ekelund, Ulf; El Ati, Jalila; Eldemire-Shearer, Denise; Eliasen, Marie; Elosua, Roberto; Erasmus, Rajiv T.; Erbel, Raimund; Erem, Cihangir; Eriksen, Louise; Eriksson, Johan G.; Escobedo-de la Pena, Jorge; Eslami, Saeid; Esmaeili, Ali; Evans, Alun; Faeh, David; Fall, Caroline H.; Faramarzi, Elnaz; Farjam, Mojtaba; Fattahi, Mohammad Reza; Felix-Redondo, Francisco J.; Ferguson, Trevor S.; Fernandez-Berges, Daniel; Ferrante, Daniel; Ferrari, Marika; Ferreccio, Catterina; Ferrieres, Jean; Foger, Bernhard; Foo, Leng Huat; Forslund, Ann-Sofie; Forsner, Maria; Fouad, Heba M.; Francis, Damian K.; Franco, Maria do Carmo; Franco, Oscar H.; Frontera, Guillermo; Fujita, Yuki; Fumihiko, Matsuda; Furusawa, Takuro; Gaciong, Zbigniew; Galvano, Fabio; Gao, Jingli; Garcia-de-la-Hera, Manoli; Garnett, Sarah P.; Gaspoz, Jean-Michel; Gasull, Magda; Gazzinelli, Andrea; Geleijnse, Johanna M.; Ghanbari, Ali; Ghasemi, Erfan; Gheorghe-Fronea, Oana-Florentina; Ghimire, Anup; Gianfagna, Francesco; Gill, Tiffany K.; Giovannelli, Jonathan; Gironella, Glen; Giwercman, Aleksander; Goltzman, David; Goncalves, Helen; Gonzalez-Chica, David A.; Gonzalez-Gross, Marcela; Gonzalez-Rivas, Juan P.; Gonzalez-Villalpando, Clicerio; Gonzalez-Villalpando, Maria-Elena; Gonzalez, Angel R.; Gottrand, Frederic; Graff-Iversen, Sidsel; Gregor, Ronald D.; Grodzicki, Tomasz; Grontved, Anders; Grosso, Giuseppe; Gruden, Gabriella; Gu, Dongfeng; Guallar-Castillon, Pilar; Guan, Ong Peng; Gudmundsson, Elias F.; Gudnason, Vilmundur; Guerrero, Ramiro; Guessous, Idris; Gunnlaugsdottir, Johanna; Gupta, Rajeev; Gutierrez, Laura; Gutzwiller, Felix; Ha, Seongjun; Hadaegh, Farzad; Haghshenas, Rosa; Hakimi, Hamid; Hambleton, Ian R.; Hamzeh, Behrooz; Hantunen, Sari; Kumar, Rachakulla Hari; Hashemi-Shahri, Seyed Mohammad; Hata, Jun; Haugsgjerd, Teresa; Hayes, Alison J.; He, Jiang; He, Yuna; Hendriks, Marleen Elisabeth; Henriques, Ana; Herrala, Sauli; Heshmat, Ramin; Hill, Allan G.; Ho, Sai Yin; Ho, Suzanne C.; Hobbs, Michael; Hofman, Albert; Homayounfar, Reza; Hopman, Wilma M.; Horimoto, Andrea R. V. R.; Hormiga, Claudia M.; Horta, Bernardo L.; Houti, Leila; Howitt, Christina; Htay, Thein Thein; Htet, Aung Soe; Htike, Maung Maung Than; Huerta, Jose Maria; Huhtaniemi, Ilpo Tapani; Huisman, Martijn; Hunsberger, Monica L.; Husseini, Abdullatif S.; Huybrechts, Inge; Hwalla, Nahla; Iacoviello, Licia; Iannone, Anna G.; Ibrahim, Mohsen M.; Wong, Norazizah Ibrahim; Iglesia, Iris; Ikeda, Nayu; Ikram, M. Arfan; Iotova, Violeta; Irazola, Vilma E.; Ishida, Takafumi; Islam, Muhammad; Ismail, Aziz Al-Safi; Iwasaki, Masanori; Jacobs, Jeremy M.; Jaddou, Hashem Y.; Jafar, Tazeen; James, Kenneth; Jamrozik, Konrad; Janszky, Imre; Janus, Edward; Jarvelin, Marjo-Riitta; Jasienska, Grazyna; Jelakovic, Ana; Jelakovic, Bojan; Jennings, Garry; Jensen, Gorm B.; Jeong, Seung-lyeal; Jha, Anjani Kumar; Jiang, Chao Qiang; Jimenez, Ramon O.; Jockel, Karl-Heinz; Joffres, Michel; Jokelainen, Jari J.; Jonas, Jost B.; Jorgensen, Torben; Joshi, Pradeep; Joukar, Farahnaz; Jozwiak, Jacek; Juolevi, Anne; Kafatos, Anthony; Kajantie, Eero O.; Kalter-Leibovici, Ofra; Kamaruddin, Nor Azmi; Kamstrup, Pia R.; Karki, Khem B.; Katz, Joanne; Kauhanen, Jussi; Kaur, Prabhdeep; Kavousi, Maryam; Kazakbaeva, Gyulli; Keil, Ulrich; Keinanen-Kiukaanniemi, Sirkka; Kelishadi, Roya; Keramati, Maryam; Kerimkulova, Alina; Kersting, Mathilde; Khader, Yousef Saleh; Khalili, Davood; Khateeb, Mohammad; Kheradmand, Motahareh; Khosravi, Alireza; Kiechl-Kohlendorfer, Ursula; Kiechl, Stefan; Killewo, Japhet; Kim, Hyeon Chang; Kim, Jeongseon; Kim, Yeon-Yong; Klumbiene, Jurate; Knoflach, Michael; Ko, Stephanie; Kohler, Hans-Peter; Kohler, Iliana; Kolle, Elin; Kolsteren, Patrick; Konig, Jurgen; Korpelainen, Raija; PaulKorrovits,; Kos, Jelena; Koskinen, Seppo; Kouda, Katsuyasu; Kowlessur, Sudhir; Kratzer, Wolfgang; Kriemler, Susi; Kristensen, Peter Lund; Krokstad, Steiner; Kromhout, Daan; Kujala, Urho M.; Kurjata, Pawel; Kyobutungi, Catherine; Laamiri, Fatima Zahra; Laatikainen, Tiina; Lachat, Carl; Laid, Youcef; Lam, Tai Hing; Lambrinou, Christina-Paulina; Lanska, Vera; Lappas, Georg; Larijani, Bagher; Latt, Tint Swe; Laugsand, Lars E.; Lazo-Porras, Maria; Lee, Jeannette; Lee, Jeonghee; Lehmann, Nils; Lehtimaki, Terho; Levitt, Naomi S.; Li, Yanping; Lilly, Christa L.; Lim, Wei-Yen; Lima-Costa, M. Fernanda; Lin, Hsien-Ho; Lin, Xu; Lin, Yi-Ting; Lind, Lars; Linneberg, Allan; Lissner, Lauren; Liu, Jing; Loit, Helle-Mai; Lopez-Garcia, Esther; Lopez, Tania; Lotufo, Paulo A.; Lozano, Jose Eugenio; Luksiene, Dalia; Lundqvist, Annamari; Lundqvist, Robert; Lunet, Nuno; Ma, Guansheng; Machado-Coelho, George L. L.; Machado-Rodrigues, Aristides M.; Machi, Suka; Madar, Ahmed A.; Maggi, Stefania; Magliano, Dianna J.; Magriplis, Emmanuella; Mahasampath, Gowri; Maire, Bernard; Makdisse, Marcia; Malekzadeh, Fatemeh; Reza Malekzadeh,; Rao, Kodavanti Mallikharjuna; Manios, Yannis; Mann, Jim; Mansour-Ghanaei, Fariborz; Manzato, Enzo; Marques-Vidal, Pedro; Martorell, Reynaldo; Mascarenhas, Luis P.; Mathiesen, Ellisiv B.; Matsha, Tandi E.; Mavrogianni, Christina; McFarlane, Shelly R.; McGarvey, Stephen T.; McLachlan, Stela; McLean, Rachael M.; McLean, Scott B.; McNulty, Breige A.; Mediene-Benchekor, Sounnia; Mehdipour, Parinaz; Mehlig, Kirsten; Mehrparvar, AmirHoushang; Meirhaeghe, Aline; Meisinger, Christa; Menezes, Ana Maria B.; Menon, Geetha R.; Merat, Shahin; Mereke, Alibek; Meshram, Indrapal I.; Metcalf, Patricia; Meyer, Haakon E.; Mi, Jie; Michels, Nathalie; Miller, Jody C.; Minderico, Claudia S.; Mini, G. K.; Miquel, Juan Francisco; Miranda, J. Jaime; Mirjalili, Mohammad Reza; Mirrakhimov, Erkin; Modesti, Pietro A.; Moghaddam, Sahar Saeedi; Mohajer, Bahram; Mohamed, MostafaK; Mohammad, Kazem; Mohammadi, Zahra; Mohammadifard, Noushin; Mohammadpourhodki, Reza; Mohan, Viswanathan; Mohanna, Salim; MohdYusoff, Muhammad Fadhli; Mohebbi, Iraj; Mohebi, Farnam; Moitry, Marie; Mollehave, Line T.; Mller, Niels C.; Molnar, Denes; Momenan, Amirabbas; Mondo, Charles K.; Monterrubio-Flores, Eric; Moosazadeh, Mahmood; Morejon, Alain; Moreno, Luis A.; Morgan, Karen; Morin, Suzanne N.; Moschonis, George; Mossakowska, Malgorzata; Mostafa, Aya; Mota, Jorge; Motlagh, Mohammad Esmaeel; Motta, Jorge; Msyamboza, Kelias P.; Muiesan, Maria L.; Muller-Nurasyid, Martina; Mursu, Jaakko; Mustafa, Norlaila; Nabipour, Iraj; Naderimagham, Shohreh; Nagel, Gabriele; Naidu, Balkish M.; Najafi, Farid; Nakamura, Harunobu; Nang, Ei Ei K.; Nangia, Vinay B.; Nauck, Matthias; Neal, William A.; Nejatizadeh, Azim; Nenko, Ilona; Nervi, Flavio; Nguyen, Nguyen D.; Quang Ngoc Nguyen,; Nieto-Martinez, Ramfis E.; Nihal, Thomas; Niiranen, Teemu J.; Ning, Guang; Ninomiya, Toshiharu; Noale, Marianna; Noboa, Oscar A.; Noto, Davide; Al Nsour, Mohannad; Nuhoglu, Irfan; O'Neill, Terence W.; O'Reilly, Dermot; Ochoa-Aviles, Angelica M.; Oh, Kyungwon; Ohtsuka, Ryutaro; Olafsson, Orn; Olie, Valerie; Oliveira, Isabel O.; Omar, Mohd Azahadi; Onat, Altan; Ong, SokKing; Ordunez, Pedro; Ornelas, Rui; Ortiz, Pedro J.; Osmond, Clive; Ostojic, Sergej M.; Ostovar, Afshin; Otero, Johanna A.; Owusu-Dabo, Ellis; Paccaud, Fred Michel; Pahomova, Elena; Pajak, Andrzej; Palmieri, Luigi; Pan, Wen-Harn; Panda-Jonas, Songhomitra; Panza, Francesco; Parnell, Winsome R.; Patel, Nikhil D.; Peer, Nasheeta; Peixoto, Sergio Viana; Peltonen, Markku; Pereira, Alexandre C.; Peters, Annette; Petersmann, Astrid; Petkeviciene, Janina; Peykari, Niloofar; Son Thai Pham,; Pichardo, Rafael N.; Pigeot, Iris; Pilav, Aida; Pilotto, Lorenza; Piwonska, Aleksandra; Pizarro, Andreia N.; Plans-Rubio, Pedro; Plata, Silvia; Pohlabeln, Hermann; Porta, Miquel; Portegies, Marileen L. P.; Poudyal, Anil; Pourfarzi, Farhad; Poustchi, Hossein; Pradeepa, Rajendra; Price, Jacqueline F.; Providencia, Rui; Puder, Jardena J.; Puhakka, Soile E.; Punab, Margus; Qorbani, Mostafa; Tran Quoc Bao,; Radisauskas, Ricardas; Rahimikazerooni, Salar; Raitakari, Olli; Rao, Sudha Ramachandra; Ramachandran, Ambady; Ramos, Elisabete; Ramos, Rafel; Rampal, Lekhraj; Rampal, Sanjay; Redon, Josep; Reganit, Paul Ferdinand M.; Revilla, Luis; Rezaianzadeh, Abbas; Ribeiro, Robespierre; Richter, Adrian; Rigo, Fernando; de Wit, Tobias F. Rinke; Rodriguez-Artalejo, Fernando; Rodriguez-Perez, Maria del Cristo; Rodriguez-Villamizar, Laura A.; Roggenbuck, Ulla; Rojas-Martinez, Rosalba; Romaguera, Dora; Romeo, Elisabetta L.; Rosengren, Annika; Roy, Joel G. R.; Rubinstein, Adolfo; Ruidavets, Jean-Bernard; Ruiz-Betancourt, Blanca Sandra; Russo, Paola; Rust, Petra; Rutkowski, Marcin; Sabanayagam, Charumathi; Sachdev, Harshpal S.; Sadjadi, Alireza; Safarpour, Ali Reza; Safiri, Saeid; Saidi, Olfa; Saki, Nader; Salanave, Benoit; Salmeron, Diego; Salomaa, Veikko; Salonen, Jukka T.; Salvetti, Massimo; Sanchez-Abanto, Jose; Sans, Susana; Santaliestra-Pasias, Alba M.; Santos, Diana A.; Santos, MariaPaula; Santos, Rute; Saramies, Jouko L.; Sardinha, Luis B.; Sarrafzadegan, Nizal; Saum, Kai-Uwe; Savva, Savvas C.; Sawada, Norie; Sbaraini, Mariana; Scazufca, Marcia; Schaan, Beatriz D.; Schargrodsky, Herman; Scheidt-Nave, Christa; Schienkiewitz, Anja; Schipf, Sabine; Schmidt, Carsten O.; Schottker, Ben; Schramm, Sara; Sebert, Sylvain; Sein, Aye Aye; Sen, Abhijit; Sepanlou, Sadaf G.; Servais, Jennifer; Shakeri, Ramin; Shalnova, Svetlana A.; Shamah-Levy, Teresa; Sharafkhah, Maryam; Sharma, Sanjib K.; Shaw, Jonathan E.; Shayanrad, Amaneh; Shi, Zumin; Shibuya, Kenji; Shimizu-Furusawa, Hana; Shin, Dong Wook; Shin, Youchan; Shirani, Majid; Shiri, Rahman; Shrestha, Namuna; Si-Ramlee, Khairil; Siani, Alfonso; Siantar, Rosalynn; Sibai, Abla M.; Santos Silva, Diego Augusto; Simon, Mary; Simons, Judith; Simons, Leon A.; Sjostrom, Michael; Skaaby, Tea; Slowikowska-Hilczer, Jolanta; Slusarczyk, Przemyslaw; Smeeth, Liam; Snijder, Marieke B.; Soderberg, Stefan; Soemantri, Agustinus; Sofat, Reecha; Solfrizzi, Vincenzo; Somi, Mohammad Hossein; Sonestedt, Emily; Sorensen, Thorkild I. A.; Jerome, Charles Sossa; Soumare, Aicha; Sozmen, Kaan; Sparrenberger, Karen; Staessen, Jan A.; Stathopoulou, Maria G.; Stavreski, Bill; Steene-Johannessen, Jostein; Stehle, Peter; Stein, Aryeh D.; Stessman, Jochanan; Stevanovic, Ranko; Stieber, Jutta; Stockl, Doris; Stokwiszewski, Jakub; Stronks, Karien; Strufaldi, Maria Wany; Suarez-Medina, Ramon; Sun, Chien-An; Sundstrom, Johan; Suriyawongpaisal, Paibul; Sy, Rody G.; Sylva, Rene Charles; Szklo, Moyses; Tai, E. Shyong; Tamosiunas, Abdonas; Tan, EngJoo; Tarawneh, Mohammed Rasoul; Tarqui-Mamani, Carolina B.; Taylor, Anne; Taylor, Julie; Tell, Grethe S.; Tello, Tania; Thankappan, K. R.; Thijs, Lutgarde; Thuesen, Betina H.; Toft, Ulla; Tolonen, Hanna K.; Tolstrup, Janne S.; Topbas, Murat; Topor-Madry, Roman; Tormo, Maria Jose; Tornaritis, Michael J.; Torrent, Maties; Torres-Collado, Laura; Traissac, Pierre; Trinh, Oanh T. H.; Truthmann, Julia; Tsugane, Shoichiro; Tulloch-Reid, Marshall K.; Tuomainen, Tomi-Pekka; Tuomilehto, Jaakko; Tybjaerg-Hansen, Anne; Tzourio, Christophe; Ueda, Peter; Ugel, Eunice; Ulmer, Hanno; Unal, Belgin; Uusitalo, Hannu M. T.; Valdivia, Gonzalo; Valvi, Damaskini; van Dam, RobM; van der Schouw, Yvonne T.; Van Herck, Koen; Hoang Van Minh,; Rossem, Lenievan; Van Schoor, Natasja M.; van Valkengoed, Irene G. M.; Vanderschueren, Dirk; Vanuzzo, Diego; Varbo, Anette; Varona-Perez, Patricia; Vasan, Senthil K.; Vatten, Lars; Vega, Tomas; Veidebaum, Toomas; Velasquez-Melendez, Gustavo; Venero-Fernandez, Silvia J.; Veronesi, Giovanni; MoniqueVerschuren, W. M.; Victora, Cesar G.; Vidiawati, Dhanasari; Viet, Lucie; Villalpando, Salvador; Vioque, Jesus; Virtanen, Jyrki K.; Visvikis-Siest, Sophie; Viswanathan, Bharathi; Vlasoff, Tiina; Vollenweider, Peter; Voutilainen, Ari; Wade, Alisha N.; Wagner, Aline; Walton, Janette; Bebakar, Wan Mohamad Wan; WanMohamud, Wan Nazaimoon; Wang, Ming-Dong; Wang, Ningli; Wang, Qian; Wang, Ya Xing; Wang, Ying-Wei; Wannamethee, S. Goya; Wedderkopp, Niels; Wei, Wenbin; Whincup, Peter H.; Widhalm, Kurt; Widyahening, Indah S.; Wiecek, Andrzej; Wijga, Alet H.; Wilks, Rainford J.; Willeit, Johann; Willeit, Peter; Wilsgaard, Tom; Wojtyniak, Bogdan; Wong-McClure, Roy A.; Wong, Andrew; Wong, Tien Yin; Woo, Jean; Woodward, Mark; Wu, Frederick C.; Wu, Shouling; Xu, Haiquan; Xu, Liang; Yan, Weili; Yang, Xiaoguang; Yasuharu, Tabara; Ye, Xingwang; Yeow, Toh Peng; Yiallouros, Panayiotis K.; Yoosefi, Moein; Yoshihara, Akihiro; You, San-Lin; Younger-Coleman, Novie O.; Yusoff, Ahmad Faudzi; Zainuddin, Ahmad A.; Zakavi, Seyed Rasoul; Zali, Mohammad Reza; Zamani, Farhad; Zambon, Sabina; Zampelas, Antonis; KoZaw, Ko; Zdrojewski, Tomasz; Vrkic, Tajana Zeljkovic; Zhang, Zhen-Yu; Zhao, Wenhua; Zhen, Shiqi; Zheng, Yingfeng; Zholdin, Bekbolat; Zhussupov, Baurzhan; Zoghlami, Nada; Cisneros, Julio Zuniga; Gregg, Edward W.; Ezzati, Majid (2020)
    High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
  • Mäkelä, Noora; Rosa-Sibakov, Natalia; Wang, Yu-Jie; Mattila, Outi; Nordlund, Emilia; Sontag-Strohm, Tuula (2021)
    There is controversy about the role of viscosity and co-migrating molecules on the bile acid binding of betaglucan. Thus, this study aimed to investigate the impact of 8-glucan molecular weight and the content of both 8-glucan and phytate on the mobility of bile acids by modelling intestinal conditions in vitro. Two approaches were used to evaluate factors underlying this binding effect. The first studied bile acid binding capacity of soluble 8-glucan using purified compounds. Viscosity of the 8-glucan solution governed mainly the mobility of bile acid since both a decrease in 8-glucan concentration and degradation of 8-glucan by enzyme hydrolysis resulted in decreased binding. The second approach investigated the trapping of bile acids in the oat bran matrix. Results suggested trapping of bile acids by the 8-glucan gel network. Additionally, hydrolysis of phytate was shown to increase bile acid binding, probably due to better extractability of 8-glucan in this sample.
  • Gurtovenko, Andrey A.; Javanainen, Matti; Lolicato, Fabio; Vattulainen, Ilpo (2019)
    Single-particle tracking (SPT) is an experimental technique that allows one to follow the dynamics of individual molecules in biological membranes with unprecedented precision. Given the importance of lipid and membrane protein diffusion in the formation of nanoscale functional complexes, it is critical to understand what exactly is measured in SPT experiments. To clarify this issue, we employed nanoscale computer simulations designed to match SPT experiments that exploit streptavidin-functionalized Au nanoparticles (AuNPs). The results show that lipid labeling interferes critically with the diffusion process; thus, the diffusion measured in SPT is a far more complex process than what has been assumed. It turns out that the influence of AuNP-based labels on the dynamics of probe lipids includes not only the AuNP-induced viscous drag that is the more significant the larger the NP but, more importantly, also the effects related to the interactions of the streptavidin linker with membrane lipids. Due to these effects, the probe lipid moves in a concerted manner as a complex with the linker protein and numerous unlabeled lipids, which can slow down the motion of the probe by almost an order of magnitude. Furthermore, our simulations show that nonlinker streptavidin tetramers on the AuNP surface are able to interact with the membrane lipids, which could potentially lead to multivalent labeling of the NPs by the probe lipids. Our results further demonstrate that in the submicrosecond time domain the motion of the probe lipid is uncorrelated with the motion of the AuNP, showing that there is a 1 mu s limit for the temporal resolution of the SPT technique. However, this limit for the temporal resolution depends on the nanoparticle size and increases rapidly with growing AuNPs. Overall, the results provide a molecular-scale framework to accurately interpret SPT data and to design protocols that minimize label-induced artifacts.
  • Wilson, Jonathan M.; Nikooienejad, Amir; Robins, Deborah A.; Roell, William C.; Riesmeyer, Jeffrey S.; Haupt, Axel; Duffin, Kevin L.; Taskinen, Marja-Riitta; Ruotolo, Giacomo (2020)
    Aim To better understand the marked decrease in serum triglycerides observed with tirzepatide in patients with type 2 diabetes, additional lipoprotein-related biomarkers were measured post hoc in available samples from the same study. Materials and Methods Patients were randomized to receive once-weekly subcutaneous tirzepatide (1, 5, 10 or 15 mg), dulaglutide (1.5 mg) or placebo. Serum lipoprotein profile, apolipoprotein (apo) A-I, B and C-III and preheparin lipoprotein lipase (LPL) were measured at baseline and at 4, 12 and 26 weeks. Lipoprotein particle profile by nuclear magnetic resonance was assessed at baseline and 26 weeks. The lipoprotein insulin resistance (LPIR) score was calculated. Results At 26 weeks, tirzepatide dose-dependently decreased apoB and apoC-III levels, and increased serum preheparin LPL compared with placebo. Tirzepatide 10 and 15 mg decreased large triglyceride-rich lipoprotein particles (TRLP), small low-density lipoprotein particles (LDLP) and LPIR score compared with both placebo and dulaglutide. Treatment with dulaglutide also reduced apoB and apoC-III levels but had no effect on either serum LPL or large TRLP, small LDLP and LPIR score. The number of total LDLP was also decreased with tirzepatide 10 and 15 mg compared with placebo. A greater reduction in apoC-III with tirzepatide was observed in patients with high compared with normal baseline triglycerides. At 26 weeks, change in apoC-III, but not body weight, was the best predictor of changes in triglycerides with tirzepatide, explaining up to 22.9% of their variability. Conclusions Tirzepatide treatment dose-dependently decreased levels of apoC-III and apoB and the number of large TRLP and small LDLP, suggesting a net improvement in atherogenic lipoprotein profile.
  • Parmar, Mayuriben; Rawson, Shaun; Scarff, Charlotte A.; Goldman, Adrian; Dafforn, Timothy R.; Muench, Stephen P.; Postis, Vincent L.G. (2018)
    The field of membrane protein structural biology has been revolutionized over the last few years with a number of high profile structures being solved using cryo-EM including Piezo, Ryanodine receptor, TRPV1 and the Glutamate receptor. Further developments in the EM field hold the promise of even greater progress in terms of greater resolution, which for membrane proteins is still typically within the 4-7 angstrom range. One advantage of a cryo-EM approach is the ability to study membrane proteins in more "native" like environments for example proteoliposomes, amphipols and nanodiscs. Recently, styrene maleic acid co-polymers (SMA) have been used to extract membrane proteins surrounded by native lipids (SMALPs) maintaining a more natural environment. We report here the structure of the Escherichia coli multidrug efflux transporter AcrB in a SMALP scaffold to sub-nm resolution, with the resulting map being consistent with high resolution crystal structures and other EM derived maps. However, both the C-terminal helix (TM12) and TM7 are poorly defined in the map. These helices are at the exterior of the helical bundle and form the greater interaction with the native lipids and SMA polymer and may represent a more dynamic region of the protein. This work shows the promise of using an SMA approach for single particle cryo-EM studies to provide sub-nm structures.