| 1. |
- Johansson, Roger, et al.
(författare)
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Pupil dilation tracks the dynamics of mnemonic interference resolution
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Mnemonic interference refers to the inability to retrieve a goal-relevant memory due to interference from goal-irrelevant memories. Understanding the causes of such interference and how it is overcome has been a central goal in the science of memory for more than a century. Here, we shed new light on this fundamental issue by tracking participants’ pupil response when they encode and retrieve memories in the face of competing goal-irrelevant memories. We show that pupil dilation systematically increased in accordance with interference from competing memory traces when participants retrieved previously learned information. Moreover, our results dissociate two main components in the pupillary response signal: an early component, which peaked in a time window where the pupillary waveform on average had its maximum peak, and a late component, which peaked towards the end of the retrieval task. We provide evidence that the early component is specifically modulated by the cognitive effort needed to handle interference from competing memory traces whereas the late component reflects general task engagement. This is the first demonstration that mnemonic interference resolution can be tracked online in the pupil signal and offers novel insight into the underlying dynamics.
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| 2. |
- de Boniface, J., et al.
(författare)
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Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial
- 2017
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference. Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1: 1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years. Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.
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| 3. |
- Dreij, Kristian, et al.
(författare)
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Cancer Risk Assessment of Airborne PAHs Based on in Vitro Mixture Potency Factors
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:15, s. 8805-8814
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Tidskriftsartikel (refereegranskat)abstract
- Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants associated with adverse human health effects including cancer. However, the risk of exposure to mixtures is difficult to estimate, and risk assessment by whole mixture potency evaluations has been suggested. To facilitate this, reliable in vitro based testing systems are necessary. Here, we investigated if activation of DNA damage signaling in vitro could be an endpoint for developing whole mixture potency factors (MPFs) for airborne PAHs. Activation of DNA damage signaling was assessed by phosphorylation of Chid and H2AX using Western blotting. To validate the in vitro approach, potency factors were determined for seven individual PAHs which were in very good agreement with established potency factors based on cancer data in vivo. Applying the method using Stockholm air PAH samples indicated MPFs with orders of magnitude higher carcinogenic potency than predicted by established in vivo-based potency factors. Applying the MPFs in cancer risk assessment suggested that 45.4 (6% of all) cancer cases per year in Stockholm are due to airborne PAHs. Applying established models resulted in <1 cancer case per year, which is far from expected levels. We conclude that our in vitro based approach for establishing MPFs could be a novel method to assess whole mixture samples of airborne PAHs to improve health risk assessment.
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| 4. |
- Jansson, John-Olov, 1954, et al.
(författare)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Tidskriftsartikel (refereegranskat)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 5. |
- Johansson, Daniel, et al.
(författare)
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Larger particle size of oat bran inhibits degradation and lowers extractability of β-glucan in sourdough bread – Potential implications for cholesterol-lowering properties in vivo
- 2018
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Ingår i: Food Hydrocolloids. - : Elsevier BV. - 0268-005X .- 1873-7137. ; 77, s. 49-56
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Tidskriftsartikel (refereegranskat)abstract
- Increased digesta viscosity is considered the mechanism underlying the cholesterol-lowering effect of oat β-glucan. Viscosity is mainly related to the molecular weight and concentration of solubilized β-glucan in the digesta and these should therefore be maintained at sufficiently high levels. Bread that includes oat bran is a potential source of β-glucan, but the baking process leads to degradation by β-glucanases present in the flours. In the current study, we investigated the effect of fermentation time as well as of particle size and content of oat bran in breads on the molecular weight, solubility and extract viscosity of β-glucan. Furthermore, we estimated the potential of the breads to have a cholesterol-lowering effect by comparison of molecular weight, solubility and extract viscosity of β-glucan with those of products known to have an effect in vivo. Longer fermentation time and smaller particles were found to lead to lower molecular weight of β-glucan. However, smaller particles also increased its extractability, leading to an overall increase in extract viscosities compared with coarse particles. Bread with the inclusion of 30% finely-milled, but not coarse oat bran was found to induce extract viscosity with the potential of producing a cholesterol-lowering effect despite more degraded β-glucan.
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| 6. |
- Laskar, Ruhina S, et al.
(författare)
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Sex specific associations in genome wide association analysis of renal cell carcinoma.
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27:10, s. 1589-1598
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
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| 7. |
- Mao, Feng, et al.
(författare)
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Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma
- 2018
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Ingår i: Oncogenesis. - : Nature Publishing Group. - 2157-9024. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a genome-wide association study showed that a single nucleotide polymorphism (SNP) —rs11706832—in intron 2 of the human LRIG1 (Leucine-rich repeats and immunoglobulin-like domains 1) gene is associated with susceptibility to glioma. However, the mechanism by which rs11706832 affects glioma risk remains unknown; additionally, it is unknown whether the expression levels of LRIG1 are a relevant determinant of gliomagenesis. Here, we investigated the role of Lrig1 in platelet-derived growth factor (PDGF)-induced experimental glioma in mice by introducing mono-allelic and bi-allelic deletions of Lrig1 followed by inducing gliomagenesis via intracranial retroviral transduction of PDGFB in neural progenitor cells. Lrig1 was expressed in PDGFB-induced gliomas in wild-type mice as assessed using in situ hybridization. Intriguingly, Lrig1-heterozygous mice developed higher grade gliomas than did wild-type mice (grade IV vs. grade II/III, p = 0.002). Reciprocally, the ectopic expression of LRIG1 in the TB107 high-grade human glioma (glioblastoma, grade IV) cell line decreased the invasion of orthotopic tumors in immunocompromised mice in vivo and reduced cell migration in vitro. Concomitantly, the activity of the receptor tyrosine kinase MET was downregulated, which partially explained the reduction in cell migration. In summary, Lrig1 is a haploinsufficient suppressor of PDGFB-driven glioma, possibly in part via negative regulation of MET-driven cell migration and invasion. Thus, for the first time, changes in physiological Lrig1 expression have been linked to gliomagenesis, whereby the SNP rs11706832 may affect glioma risk by regulating LRIG1 expression.
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| 8. |
- Pärnamets, Philip, et al.
(författare)
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How information availability interacts with visual attention during judgment and decision tasks
- 2016
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Ingår i: Journal of Behavioral Decision Making. - : Wiley. - 1099-0771 .- 0894-3257. ; 29:2-3, s. 218-231
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Tidskriftsartikel (refereegranskat)abstract
- Decisions in front of a supermarket shelf probably involve a mix of visually available information and associated memories – and interactions between those two. Several cognitive processes, such as decision-making, search and various judgments, are therefore likely to co-occur, and each process will influence visual attention. We conducted two eye-tracking experiments capturing parts of these features by having participants make either judgments or decisions concerning products that had been previously encoded. Half the time participants made their choices with full information about the available products and half the time with crucial task-relevant information removed. By comparing participants’ use of visual attention during decisions and search- and memory-based judgments, respectively, we can better understand how visual attention is differently employed between tasks and how it depends on the visual environment. We found that participants’ visual attention during decisions is sensitive to evaluations already made during encoding and strongly characterized by preferential looking to the options later to be chosen. When the task environment is rich enough, participants engage in advanced integrative visual behavior and improve their decision quality. In contrast, visual attention during judgments made on the same products reflects a search-like behavior when all information is available and a more focused type of visual behavior when information is removed. Our findings contribute not only to the literature on how visual attention is used during decision-making but also to methodological questions concerning how to measure and identify task-specific features of visual attention in ecologically valid ways.
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