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Sökning: WFRF:(Dahlman A. S.)

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1.
  • Yusuf, D, et al. (författare)
  • The transcription factor encyclopedia
  • 2012
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
  • Tidskriftsartikel (refereegranskat)
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  • Stahel, P, et al. (författare)
  • Evaluation of the Genetic Association Between Adult Obesity and Neuropsychiatric Disease
  • 2019
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 68:12, s. 2235-2246
  • Tidskriftsartikel (refereegranskat)abstract
    • Extreme obesity (EO) (BMI >50 kg/m2) is frequently associated with neuropsychiatric disease (NPD). As both EO and NPD are heritable central nervous system disorders, we assessed the prevalence of protein-truncating variants (PTVs) and copy number variants (CNVs) in genes/regions previously implicated in NPD in adults with EO (n = 149) referred for weight loss/bariatric surgery. We also assessed the prevalence of CNVs in patients referred to University College London Hospital (UCLH) with EO (n = 218) and obesity (O) (BMI 35–50 kg/m2; n = 374) and a Swedish cohort of participants from the community with predominantly O (n = 161). The prevalence of variants was compared with control subjects in the Exome Aggregation Consortium/Genome Aggregation Database. In the discovery cohort (high NPD prevalence: 77%), the cumulative PTV/CNV allele frequency (AF) was 7.7% vs. 2.6% in control subjects (odds ratio [OR] 3.1 [95% CI 2–4.1]; P < 0.0001). In the UCLH EO cohort (intermediate NPD prevalence: 47%), CNV AF (1.8% vs. 0.9% in control subjects; OR 1.95 [95% CI 0.96–3.93]; P = 0.06) was lower than the discovery cohort. CNV AF was not increased in the UCLH O cohort (0.8%). No CNVs were identified in the Swedish cohort with no NPD. These findings suggest that PTV/CNVs, in genes/regions previously associated with NPD, may contribute to NPD in patients with EO.
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  • Dahlman, A., et al. (författare)
  • Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3
  • 2010
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 13:4, s. 369-375
  • Tidskriftsartikel (refereegranskat)abstract
    • We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.
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  • Uusitupa, M., et al. (författare)
  • Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome : a randomized study (SYSDIET)
  • 2013
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 274:1, s. 52-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24weeks in individuals with features of metabolic syndrome (mean age 55years, BMI 31.6kgm-2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmolL-1 95% CI -0.35; -0.01, P=0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P=0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P=0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37ngL-1, P= 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P=0.049) and magnesium (mg, -0.23, -0.41; -0.05, P=0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.
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  • Lundholm, L, et al. (författare)
  • The estrogen receptor {alpha}-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms
  • 2008
  • Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 199:2, s. 275-286
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to validate the role of estrogen receptor alpha (ERalpha) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERalpha-selective agonist propyl pyrazole triol (PPT) or 17beta-estradiol (E(2)) in ob/ob mice. Female ob/ob mice were treated with PPT, E(2) or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPT and E(2) treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E(2) treatment. However, PPT and E(2) had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E(2) treatment. In the liver, treatment with E(2) and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPT exerts anti-diabetic effects, and these effects are mediated via ERalpha.
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  • Bryzgalova, G, et al. (författare)
  • Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver
  • 2006
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 49:3, s. 588-597
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: We used oestrogen receptor-alpha (ER alpha) knockout (ERKO) and receptor-beta (ER beta) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis. Methods: Endogenous glucose production (EGP) was measured in ERKO mice using a euglycaemic-hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets. In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes. Genome-wide expression profiles were analysed by high-density oligonucleotide microarray assay, and the expression of the genes encoding steroyl-CoA desaturase and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR. Results: ERKO mice had higher fasting blood glucose, plasma insulin levels and IGT. The plasma leptin level was increased, while the adiponectin concentration was decreased in ERKO mice. Levels of both glucose- and arginine-induced insulin secretion from isolated islets were similar in ERKO and wild-type mice. The euglycaemic-hyperinsulinaemic clamp revealed that suppression of EGP by increased insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic insulin resistance. Microarray analysis revealed that in ERKO mice, the genes involved in hepatic lipid biosynthesis were upregulated, while genes involved in lipid transport were downregulated. Notably, hepatic Lepr expression was decreased in ERKO mice. In vitro studies showed a modest decrease in insulin-mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release. Conclusions/interpretation: We conclude that oestrogens, acting via ER alpha, regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity, which can be due to the upregulation of lipogenic genes via the suppression of Lepr expression.
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  • Hanson, L A, et al. (författare)
  • Sensitization and development of tolerance via the gut.
  • 1993
  • Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - 0905-6157. ; 4:3 Suppl, s. 16-20
  • Tidskriftsartikel (refereegranskat)
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  • Kerr, A. G., et al. (författare)
  • The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase
  • 2022
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The pleiotropic function of long noncoding RNAs is well recognized, but their direct role in governing metabolic homeostasis is less understood. Here, we describe a human adipocyte-specific lncRNA, ADIPINT, that regulates pyruvate carboxylase, a pivotal enzyme in energy metabolism. We developed an approach, Targeted RNA-protein identification using Orthogonal Organic Phase Separation, which identifies that ADIPINT binds to pyruvate carboxylase and validated the interaction with electron microscopy. ADIPINT knockdown alters the interactome and decreases the abundance and enzymatic activity of pyruvate carboxylase in the mitochondria. Reduced ADIPINT or pyruvate carboxylase expression lowers adipocyte lipid synthesis, breakdown, and lipid content. In human white adipose tissue, ADIPINT expression is increased in obesity and linked to fat cell size, adipose insulin resistance, and pyruvate carboxylase activity. Thus, we identify ADIPINT as a regulator of lipid metabolism in human white adipocytes, which at least in part is mediated through its interaction with pyruvate carboxylase. 
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  • Pelkmans, L., et al. (författare)
  • Monitoring the Impact of Sustainability Certification in Relation to Biomass Use for Energy
  • 2012
  • Ingår i: EUBCE 2012 proceedings. - 9788889407547 ; , s. 2013-2018
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Since the public has expressed concern about unintended consequences associated with potentially unsustainable biomass production and use for energy (or biofuels), producers of biomass feedstocks in the private sector as well as governmental and non-governmental organisations have initiated many generally unlinked efforts to define 'sustainable' bioenergy production and supply chains. These 'sustainability' standards may be implemented through certification systems involving 3rd party audit, and influence production systems and trade of bioenergy products from producers to consumers of ‘green' energy. At present numerous biomass and biofuel sustainability certification systems are being developed or implemented by a variety of private and public organisations. Systems are applicable to different feedstock production sectors (forests, agricultural crops), different bioenergy products (relatively unprocessed forest residues, ethanol, biodiesel, electricity), and whole or segments of supply chains (production system, chain of custody from growers to energy consumers). It is expected that such a wide range of systems, developed largely without coordination among the organisations involved, could be problematic for all stakeholders along the supply chain in individual sectors and for those involved in deployment of bioenergy systems globally. These are individual feedstock producers, companies and commodity sectors that must comply with these systems either to maintain market access and share or to comply with legislative mandates, and also consumers who prefer to purchase certified green energy, and regulatory agencies and local to national governments that may be involved in enforcing sustainability standards. The potential for confusion among the actors, depression of markets, and unnecessary restrictions on sustainable trade seems high. Within IEA Bioenergy a strategic study was initiated between Task 40, Task 43 and Task 38 to monitor the actual implementation process of sustainability certification of bioenergy, evaluate how stakeholders are affected by certification initiatives, quantify the anticipated impact on worldwide bioenergy trade, assess the level of coordination among schemes, and make recommendations to remove barriers which may depress markets and reduce sustainable trade. Interaction with different stakeholder groups is one of the main objectives of this study, so we anticipate the recommendations being representative of the whole bioenergy certification sector and therefore having high potential to improve an otherwise uncoordinated interest in ensuring bioenergy trade is sustainable.
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  • Arvidsson, Elin, et al. (författare)
  • Exercise training and physiological responses to acute stress: study protocol and methodological considerations of a randomised controlled trial
  • 2018
  • Ingår i: BMJ Open Sport & Exercise Medicine. - : BMJ. - 2055-7647. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This paper describes the protocol and methodological prerequisites for a randomised controlled exercise intervention. Selected baseline data from the study are also presented, demonstrating some methodological challenges related to exercise intervention trials. The aim of the trial was to study the effects of exercise training on physiological responses to acute psychosocial stress in untrained individuals. Methods: Individuals with a low level of physical activity were invited to participate in an exercise intervention lasting for 6 months. A total of 119 participants were included and went through a peak oxygen uptake test and a psychosocial stress test at baseline. Adrenocorticotropic hormone (ACTH) and cortisol were measured in connection to the stress test to identify the physiological response. Results: Almost 90% of the participants reported themselves as untrained, but results from the objectively measured oxygen uptake did not seem to correspond to the reported sedentary lifestyle. The primary outcome measures at baseline varied between individuals. The mean change from pre-test to peak value was 214% for ACTH and 94% for cortisol. Of these, 13 individuals did not respond in ACTH and/or and cortisol. Discussion: Supposedly untrained individuals seeking participation in an exercise intervention might not be as untrained as they report, a methodological consideration of importance when evaluating the effects of training. Another important consideration is related to the primary outcome measure, which should be measurable and possible to affect. Absence of reaction at baseline means that changes can only be detected as an increased reaction.
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  • Bryzgalova, G, et al. (författare)
  • Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice
  • 2008
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 295:4, s. E904-E912
  • Tidskriftsartikel (refereegranskat)abstract
    • The high-fat diet (HFD)-fed mouse is a model of obesity, impaired glucose tolerance, and insulin resistance. The main objective of this study was to elucidate the molecular mechanisms underlying the antidiabetogenic and weight-lowering effects of 17β-estradiol (E2) in this mouse model. C57BL/6 female mice (8 wk old) were fed on a HFD for 10 mo. E2, given daily (50 μg/kg sc) during the last month of feeding, decreased body weight and markedly improved glucose tolerance and insulin sensitivity. Plasma levels of insulin, leptin, resistin, and adiponectin were decreased. We demonstrated that E2treatment decreased the expression of genes encoding resistin and leptin in white adipose tissue (WAT), whereas adiponectin expression was unchanged. Furthermore, in WAT we demonstrated decreased expression levels of sterol regulatory element-binding protein 1c (SREBP1c) and its lipogenic target genes, such as fatty acid synthase and stearoyl-CoA desaturase 1 (SCD1). In the liver, the expression levels of transcription factors such as liver X receptor α and SREBP1c were not changed by E2treatment, but the expression of the key lipogenic gene SCD1 was reduced. This was accompanied by decreased hepatic triglyceride content. Importantly, E2decreased the hepatic expression of glucose-6-phosphatase (G-6-Pase). We conclude that E2treatment exerts antidiabetic and antiobesity effects in HFD mice and suggest that this is related to decreased expression of lipogenic genes in WAT and liver and suppression of hepatic expression of G-6-Pase. Decreased plasma levels of resistin probably also play an important role in this context.
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  • Combs, Elizabeth K., et al. (författare)
  • Physiological and Cognitive Performance in F-22 Pilots During Day and Night Flying
  • 2021
  • Ingår i: Aerospace Medicine and Human Performance. - : Aerospace Medical Association. - 2375-6314 .- 2375-6322. ; 92:5, s. 303-311
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Many workers routinely transition between day and night shifts—including pilots, where night flights are commonly considered more stressful. The physiological toll from this transition is not fully understood, though fatigue is a factor in many aviation accidents. This research investigated the changes in physiological markers of stress and cognitive performance as F-22 pilots transitioned from day flying to night flying. methods: There were 17 fully-qualified F-22 pilots who took part in a 2-wk data collection using salivary swabs, wrist-worn activity monitors, the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) inventory, and a go/no-go (GNG) test. results: No differences were found in comparing day and night flying on the GNG reaction time/accuracy, NASA-TLX scores, or sleep quantity. Cortisol levels were significantly higher than civilian levels in all experimental conditions and control days. Participants had higher than predicted cortisol levels postflight in the day-flying condition and lower than predicted cortisol levels postflight in the night-flying condition, relative to levels from control day patterns. We also found smaller changes in cortisol (pre- to postflight) in the day-flying condition for those with more F-22 experience. Finally, we found a negative correlation between Perceived Stress Scale scores and age of pilots (r 5 -20.72). discussion: We hypothesized that the night-flying environment would be more stressful, but our results disputed this claim. Our results suggest day flying elicits more of a stress response; however, a larger sample size is required to verify results. Preliminary findings of potential stress adaptation may suggest stress adaptation in the F-22 community needs further investigation.
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  • Dobbins, T, et al. (författare)
  • Information architecture for fast response craft - Command & control & human systems integration
  • 2013
  • Ingår i: RINA, Royal Institution of Naval Architects - International Conference on SURV 2013, Surveillance Search and Rescue Craft. - 9781909024137 ; , s. 117-120
  • Konferensbidrag (refereegranskat)abstract
    • Command & Control (C2) is required for safe and effective maritime operations. To facilitate effective decision-making and C2, it is essential that the crew can access the required information. It is therefore essential that the appropriate information architecture is used. Navigation, being an essential aspect of C2, has seen a radical change from paper charts and individual instruments to computer systems capable of sophisticated data fusion to provide enhanced situational awareness. The development of the required information architecture is not a software/engineering issue, but rather lies within the human factors domain as it requires an understanding of how humans perceive information, how they use mental models and subsequently make safe and effective decisions. © 2013: The Royal Institution of Naval Architects.
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  • Hanson, Lars Å, et al. (författare)
  • Immunological mechanisms of the gut.
  • 1995
  • Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - 0905-6157. ; 6 Suppl 8, s. 7-12
  • Tidskriftsartikel (refereegranskat)
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  • Jonsdottir, Ingibjörg H, 1966, et al. (författare)
  • Endocrine and immunological aspects of burnout: a narrative review
  • 2019
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 180:3
  • Forskningsöversikt (refereegranskat)abstract
    • Burnout has several different definitions, and attempts have been made to discriminate between burnout as a psychological construct and burnout as a clinical entity. A large body of research has focused on elucidating the biological link between stress exposure and burnout and/or finding a clinically usable biomarker for burnout. The objective of this narrative review is to summarize the main end ocrine and immune findings in relation to burnout. The literature has primarily focused on dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. However, albeit the large body of studies, it cannot be concluded that clear effects are seen on HPA axis function in people with burnout. The HPA axis and anabolic acute reactivity to stress might be affected in clinical burnout. Plausible, effects of chronic stress might rather be seen when measuring responses to acute stress rather than resting state hormonal levels. Studies on other hormones, including thyroid hormones, prolactin and growth hormone in burnout subjects are inconclusive. It is important to note that this field is faced with many methodological challenges, one being the diurnal and pulsatile nature of many of the hormones of interest, including cortisol, which is not always considered. Another challenge is the heterogeneity regarding definitions and measurements of stress and burnout. Existing studies on burnout and immune function are heterogeneous regarding the results and no firm conclusion can be made if clinically relevant immune changes are present in burnout subjects. An overall conclusion is that existing research cannot confirm any homogenous reliable endocrinological or immunological changes related to burnout.
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  • Kulyte, A, et al. (författare)
  • MicroRNA profiling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia
  • 2014
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 306:3, s. E267-E274
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer cachexia is associated with pronounced adipose tissue loss due to, at least in part, increased fat cell lipolysis. MicroRNAs (miRNAs) have recently been implicated in controlling several aspects of adipocyte function. To gain insight into the possible impact of miRNAs on adipose lipolysis in cancer cachexia, global miRNA expression was explored in abdominal subcutaneous adipose tissue from gastrointestinal cancer patients with ( n = 10) or without ( n = 11) cachexia. Effects of miRNA overexpression or inhibition on lipolysis were determined in human in vitro differentiated adipocytes. Out of 116 miRNAs present in adipose tissue, five displayed distinct cachexia-associated expression according to both microarray and RT-qPCR. Four (miR-483–5p/-23a/-744/-99b) were downregulated, whereas one (miR-378) was significantly upregulated in cachexia. Adipose expression of miR-378 associated strongly and positively with catecholamine-stimulated lipolysis in adipocytes. This correlation is most probably causal because overexpression of miR-378 in human adipocytes increased catecholamine-stimulated lipolysis. In addition, inhibition of miR-378 expression attenuated stimulated lipolysis and reduced the expression of LIPE, PLIN1, and PNPLA2, a set of genes encoding key lipolytic regulators. Taken together, increased miR-378 expression could play an etiological role in cancer cachexia-associated adipose tissue loss via effects on adipocyte lipolysis.
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  • Lindblad, M. S., et al. (författare)
  • Modified galactoglucomannans from forestry waste-water for films and hydrogels
  • 2009
  • Ingår i: American Chemical Society Symposium Series (ACS). - Washington DC : American Chemical Society. - 0097-6156 .- 1947-5918. ; 1017, s. 185-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemicelluloses are among the most abundant natural polymers in the world and are consequently a potential source for sustainable materials, that has so far been underexploited. Galactoglucomannans are the principal hemicelluloses in softwoods and can be found in, for example, industrial wood processing waste-water. Currently, we are investigating the fractionation and purification of O-acetylgalactoglucomannans from newsprint and fiberboard mill waste-waters, as well as the preparation of new barrier films with low oxygen permeation and hydrogel materials from the fractions obtained. Self-supporting films have been formed by solution-casting. Interesting oxygen barrier and mechanical strength properties were achieved for films obtained from a physical blend of O-acetyl-galactoglucomannan and either alginate or carboxymethylcellulose. To create oxygen barrier films with high resistance towards moisture, benzylated derivatives of O-acetyl-galactoglucomannan were made. A hydrogel is a polymeric material that swells in water but does not dissolve, valuable for applications including drug delivery. In order to obtain the right properties, we performed tailored cross-linking to create a flexible network structure. The chemical modification procedure involves a methacrylation reaction carried out under mild conditions. Herein we review past work and present some new data on fractionation and purification of galactoglucomannans. © 2009 American Chemical Society.
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  • Modigh, C M, et al. (författare)
  • Time to pregnancy among partners of men exposed to di(2-ethylhexyl)phthalate
  • 2002
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140. ; 28:6, s. 418-428
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This study assessed paternal occupational exposure to di(2-ethylhexyl)phthalate (DEHP) in association with reduced fertility. Methods Men working in three plants with DEHP exposure were studied retrospectively. Male and female employees and their partners were invited to participate if they had reported a pregnancy or an attempt to achieve a pregnancy. Postal questionnaires and telephone interviews were used to collect additional data from the men and women, respectively. Information on time to pregnancy was eligible for 326 pregnancies fathered by 193 men. Male exposure to DEHP during every month of their time to pregnancy was classified into one of three exposure categories. The exposure ranged from <0.1 to 2.1 mg/ml(3). The fathers of only four pregnancies had DEHP exposure of >0.5 mg/m(3) during the time to pregnancy. The pregnancies of employed women with unexposed partners or pregnancies of employed men unexposed during the time to pregnancy formed the reference group. Results The fecundability ratio for time to pregnancy was 1.07 [95% confidence interval (95% Cl) 0.84-1.351 for those with low exposure and 0.97 (95% CI 0.70-1.33) for the highly exposed after adjustment for the father's age, mother's age, and length of recall. When the analyses were restricted to first pregnancy, the fecundability ratio was 1.13 (95% Cl 0.83-1.56) for low exposure and 1.02 (95% Cl 0.66-1.59) for high exposure. Conclusions Time to pregnancy is not prolonged among couples with paternal exposure to DEHP at a mean exposure level of <0.5 mg/ml.
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  • Ordqvist, A., et al. (författare)
  • Information and repetition change children's visual strategies when viewing magic tricks and without gaze cues
  • 2013
  • Ingår i: Perceptual and Motor Skills. - : SAGE Publications. - 0031-5125 .- 1558-688X. ; 116:1, s. 144-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Gaze cues and direct gaze attract visual attention. However, few studies have explored visual cues in children within realistic contexts. The effect of information and repetitive stimulus presentation has not been thoroughly studied with dynamic stimuli. The aim of the present study was to investigate how information affects the visual strategies of children measured by the number of fixations on certain areas of interest and their durations. Furthermore, this study examined the effect of gaze cues and direct gaze. In two consecutive experiments, children's visual strategies when viewing magic tricks were measured by an eye tracker. Gaze cues were only present in Experiment 1. The results showed that repetitive stimulus presentation and information caused children to change their visual strategies when viewing magic tricks with and without gaze cues. However, the effect was larger when the gaze cues were not present. These findings in children were similar to those in adults.
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  • Zhu, J, et al. (författare)
  • The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.
  • 2014
  • Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 33:34, s. 4340-4351
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen receptor α (ERα) is initially expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression by regulating the transcription of genes linked to cell proliferation. ERα status is of clinical importance, as ERα-positive breast cancers can be successfully treated by adjuvant therapy with antiestrogens or aromatase inhibitors. Complications arise from the frequent development of drug resistance that might be caused by multiple alterations, including components of ERα signaling, during tumor progression and metastasis. Therefore, insights into the molecular mechanisms that control ERα expression and stability are of utmost importance to improve breast cancer diagnostics and therapeutics. Here we report that the atypical E3 ubiquitin ligase RNF31 stabilizes ERα and facilitates ERα-stimulated proliferation in breast cancer cell lines. We show that depletion of RNF31 decreases the number of cells in the S phase and reduces the levels of ERα and its downstream target genes, including cyclin D1 and c-myc. Analysis of data from clinical samples confirms correlation between RNF31 expression and the expression of ERα target genes. Immunoprecipitation indicates that RNF31 associates with ERα and increases its stability and mono-ubiquitination, dependent on the ubiquitin ligase activity of RNF31. Our data suggest that association of RNF31 and ERα occurs mainly in the cytosol, consistent with the lack of RNF31 recruitment to ERα-occupied promoters. In conclusion, our study establishes a non-genomic mechanism by which RNF31 via stabilizing ERα levels controls the transcription of estrogen-dependent genes linked to breast cancer cell proliferation.
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