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8. |
- Ahmed, M., et al.
(author)
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Search for the lepton-family-number nonconserving decay μ +→e +γ
- 2002
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In: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
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Journal article (peer-reviewed)abstract
- The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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9. |
- Birnir, Bryndis, et al.
(author)
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Rapid desensitization of alpha 1 beta 1 GABA A receptors expressed in Sf9 cells under optimized conditions.
- 1995
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In: Journal of Membrane Biology. - 0022-2631 .- 1432-1424. ; 148:2, s. 193-202
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Journal article (peer-reviewed)abstract
- alpha 1 and beta 1 subunits of human GABA A receptors were expressed in Sf9 cells using the Sf9-baculovirus system. Better expression was obtained by manipulating the system. Cell growth phase at the time of infection determined the practical range of virus titre, the period postinfection during which cells were useful for signal detection and the maximal current obtained. Cells in the early exponential phase were relatively insensitive to multiplicity of infection (MOI) whereas cells in the mid- to late-exponential phase were highly dependent on MOI and they responded with the largest Cl- current generated by GABA. Channels activated by GABA were chloride-selective. Half the maximum peak whole-cell current was obtained with 11 microM GABA. The time course of Cl- currents activated by saturating GABA concentrations in cells infected with alpha 1 beta 1-recombinant viruses was examined employing a rapid perfusion system which allowed whole-cell solution exchange in less than 1 msec. The current decay could be fitted by 3 to 4 exponentials for the first 8 sec. The initial fast current decrease had a time constant of about 23 msec. No voltage dependence of time constants was detected but the whole-cell IV relation showed outward rectification. Currents were depressed by bicuculline, penicillin and picrotoxin and potentiated by pentobarbitone.
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10. |
- Kennedy, S. A., et al.
(author)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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- Mariz, FC, et al.
(author)
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Peak neutralizing and cross-neutralizing antibody levels to human papillomavirus types 6/16/18/31/33/45/52/58 induced by bivalent and quadrivalent HPV vaccines
- 2020
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In: NPJ vaccines. - : Springer Science and Business Media LLC. - 2059-0105. ; 5:1, s. 14-
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Journal article (peer-reviewed)abstract
- We performed an independent comparison of neutralizing and cross-neutralizing antibody (ab) levels seven months after initiation of three-dose, six-month vaccination schedules with the bivalent and quadrivalent human papillomavirus (HPV) vaccines in adolescent Finnish and Indian females, respectively. We used a semi-automated Pseudovirion-Based Neutralization Assay and observed significantly higher HPV16/18 peak ab-levels in bivalent as compared to quadrivalent vaccine recipients. Bivalent vaccine induced cross-neutralizing HPV31/33/45/52/58 antibodies significantly more frequently and to higher levels than the quadrivalent vaccine. The correlation of bivalent vaccine-induced HPV45 ab-levels with HPV16/18 ab-levels was stronger than that of corresponding quadrivalent vaccine-induced ab-levels, suggesting a qualitatively different cross-reactive response. Our findings on the comparison of the immunogenicity of two HPV vaccine tested in two different populations indicate that further head-to-head studies are warranted.
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- Palafox, B., et al.
(author)
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Does greater individual social capital improve the management of hypertension? Cross-national analysis of 61 229 individuals in 21 countries
- 2017
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In: Bmj Global Health. - : BMJ. - 2059-7908. ; 2:4
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Journal article (peer-reviewed)abstract
- Introduction Social capital, characterised by trust, reciprocity and cooperation, is positively associated with a number of health outcomes. We test the hypothesis that among hypertensive individuals, those with greater social capital are more likely to have their hypertension detected, treated and controlled. Methods Cross-sectional data from 21 countries in the Prospective Urban and Rural Epidemiology study were collected covering 61 229 hypertensive individuals aged 35-70 years, their households and the 656 communities in which they live. Outcomes include whether hypertensive participants have their condition detected, treated and/or controlled. Multivariate statistical models adjusting for community fixed effects were used to assess the associations of three social capital measures: (1) membership of any social organisation, (2) trust in other people and (3) trust in organisations, stratified into high-income and low-income country samples. Results In low-income countries, membership of any social organisation was associated with a 3% greater likelihood of having one's hypertension detected and controlled, while greater trust in organisations significantly increased the likelihood of detection by 4%. These associations were not observed among participants in high-income countries. Conclusion Although the observed associations are modest, some aspects of social capital are associated with better management of hypertension in low-income countries where health systems are often weak. Given that hypertension affects millions in these countries, even modest gains at all points along the treatment pathway could improve management for many, and translate into the prevention of thousands of cardiovascular events each year.
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- Swami, Viren, et al.
(author)
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The Attractive Female Body Weight and Female Body Dissatisfaction in 26 Countries Across 10 World Regions : Results of the International Body Project I
- 2010
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In: Personality and Social Psychology Bulletin. - : Sage Publications. - 0146-1672 .- 1552-7433. ; 36:3, s. 309-325
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Journal article (peer-reviewed)abstract
- This study reports results from the first International Body Project (IBP-I), which surveyed 7,434 individuals in 10 major world regions about body weight ideals and body dissatisfaction. Participants completed the female Contour Drawing Figure Rating Scale (CDFRS) and self-reported their exposure to Western and local media. Results indicated there were significant cross-regional differences in the ideal female figure and body dissatisfaction, but effect sizes were small across high-socioeconomic-status (SES) sites. Within cultures, heavier bodies were preferred in low-SES sites compared to high-SES sites in Malaysia and South Africa (ds = 1.94-2.49) but not in Austria. Participant age, body mass index (BMI), and Western media exposure predicted body weight ideals. BMI and Western media exposure predicted body dissatisfaction among women. Our results show that body dissatisfaction and desire for thinness is commonplace in high-SES settings across world regions, highlighting the need for international attention to this problem.
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17. |
- Tierney, M L, et al.
(author)
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Effects of mutating leucine to threonine in the M2 segment of alpha1 and beta1 subunits of GABAA alpha1beta1 receptors.
- 1996
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In: Journal of Membrane Biology. - 0022-2631 .- 1432-1424. ; 154:1, s. 11-21
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Journal article (peer-reviewed)abstract
- The conserved leucine residues at the 9' positions in the M2 segments of alpha1 (L264) and beta1 (L259) subunits of the human GABAA receptor were replaced with threonine. Normal or mutant alpha1 subunits were co-expressed with normal or mutant beta1 subunits in Sf9 cells using the baculovirus/Sf9 expression system. Cells in which one or both subunits were mutated had a higher "resting" chloride conductance than cells expressing wild-type alpha1beta1 receptors. This chloride conductance was blocked by 10 mM penicillin, a recognized blocker of GABAA channels, but not by bicuculline (100 microm) or picrotoxin (100 microm) which normally inhibit the chloride current activated by GABA: nor was it potentiated by pentobarbitone (100 microM). In cells expressing wild-type beta1 with mutated alpha1 subunits, an additional chloride current could be elicited by GABA but the rise time and decay were slower than for wild-type alpha1beta1 receptors. In cells expressing mutated beta1 subunits with wild-type or mutated alpha1 subunits (alphabeta(L9'T) and alpha(L9'T)beta(L9'T)), no response to GABA could be elicited: this was not due to an absence of GABAA receptors in the plasmalemma because the cells bound [3H]-muscimol. It was concluded that in GABAA channels containing the L9'T mutation in the beta1 subunit, GABA-binding does not cause opening of channels, and that the L9'T mutation in either or both subunits gives an open-channel state of the GABAA receptor in the absence of ligand.
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18. |
- Wang, Chao, et al.
(author)
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The role of turbulence in high-mass star formation: Subsonic and transonic turbulence are ubiquitously found at early stages
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 681
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Journal article (peer-reviewed)abstract
- Context. Traditionally, supersonic turbulence is considered to be one of the most likely mechanisms slowing the gravitational collapse in dense clumps, thereby enabling the formation of massive stars. However, several recent studies have raised differing points of view based on observations carried out with sufficiently high spatial and spectral resolution. These studies call for a re-evaluation of the role turbulence plays in massive star-forming regions. Aims. Our aim is to study the gas properties, especially the turbulence, in a sample of massive star-forming regions with sufficient spatial and spectral resolution, which can both resolve the core fragmentation and the thermal line width. Methods. We observed NH3 metastable lines with the Very Large Array (VLA) to assess the intrinsic turbulence. Results. Analysis of the turbulence distribution histogram for 32 identified NH3 cores reveals the presence of three distinct components. Furthermore, our results suggest that (1) sub-and transonic turbulence is a prevalent (21 of 32) feature of massive star-forming regions and those cold regions are at early evolutionary stage. This investigation indicates that turbulence alone is insufficient to provide the necessary internal pressure required for massive star formation, necessitating further exploration of alternative candidates; and (2) studies of seven multi-core systems indicate that the cores within each system mainly share similar gas properties and masses. However, two of the systems are characterized by the presence of exceptionally cold and dense cores that are situated at the spatial center of each system. Our findings support the hub-filament model as an explanation for this observed distribution.
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19. |
- Amann, F., et al.
(author)
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A search for murarregamma at the level of 10-13
- 1991
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In: Proceedings of the 25th International Conference on High Energy Physics. - 9810024347 ; , s. 1070-1071
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Conference paper (peer-reviewed)abstract
- The MEGA experiment, which is a search for the decay murarregamma with a branching ratio sensitivity of about 10-13, employs highly modular, fast detectors, state-of-the-art electronics, and a staged trigger with on-line filters. The detectors are contained in a 1.5-T solenoidal field produced by a superconducting magnet. Positrons are confined to the central region and are measured by a set of thin MWPCs. Photons are measured by one of four layers of pair spectrometers in the outer region. Most aspects of the design have been validated in engineering runs; data taking will begin in 1990 with much of the electron arm and one pair spectrometer layer installed.
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22. |
- Fijoł, Natalia, et al.
(author)
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3D-printed monolithic biofilters based on a polylactic acid (PLA) - hydroxyapatite (HAp) composite for heavy metal removal from an aqueous medium
- 2021
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In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 11:51, s. 32408-32418
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Journal article (peer-reviewed)abstract
- High flux, monolithic water purification filters based on polylactic acid (PLA) functionalised with fish scale extracted hydroxyapatite (HAp) were prepared by solvent-assisted blending and thermally induced phase separation (TIPS), followed by twin-screw extrusion into filaments and processed via three-dimensional (3D) printing. The printed filters with consistent pore geometry and channel interconnectivity as well as homogenous distribution of HAp in the PLA matrix showed adsorption capabilities towards heavy metals i.e. cadmium (Cd) and lead (Pb) with maximum adsorption capacity of 112.1 mg gHAp−1 and 360.5 mg gHAp−1 for the metal salt of Pb and Cd, respectively. The adsorption was found to be driven by a combination of ion exchange, dissolution and precipitation on HAp and surface complexation.
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- Frosi, Y, et al.
(author)
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Engineering an autonomous VH domain to modulate intracellular pathways and to interrogate the eIF4F complex
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4854-
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Journal article (peer-reviewed)abstract
- An attractive approach to target intracellular macromolecular interfaces and to model putative drug interactions is to design small high-affinity proteins. Variable domains of the immunoglobulin heavy chain (VH domains) are ideal miniproteins, but their development has been restricted by poor intracellular stability and expression. Here we show that an autonomous and disufhide-free VH domain is suitable for intracellular studies and use it to construct a high-diversity phage display library. Using this library and affinity maturation techniques we identify VH domains with picomolar affinity against eIF4E, a protein commonly hyper-activated in cancer. We demonstrate that these molecules interact with eIF4E at the eIF4G binding site via a distinct structural pose. Intracellular overexpression of these miniproteins reduce cellular proliferation and expression of malignancy-related proteins in cancer cell lines. The linkage of high-diversity in vitro libraries with an intracellularly expressible miniprotein scaffold will facilitate the discovery of VH domains suitable for intracellular applications.
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25. |
- Jayasree, R. S., et al.
(author)
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Raman and infrared spectral analysis of corrosion products on zinc NaZn4Cl(OH)(6)SO4-6H(2)O and Zn4Cl2(OH)(4)SO4 center dot 5H(2)O
- 2006
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In: Materials Chemistry and Physics. - : Elsevier BV. - 0254-0584 .- 1879-3312. ; 99:03-feb, s. 474-478
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Journal article (peer-reviewed)abstract
- Two corrosion products of zinc namely NaZn4Cl(OH)(6)SO4 center dot 6H(2)O which occurs mainly in marine and traffic environments and Zn4Cl2(OH)(4)SO4 center dot 5H(2)O which occurs in industrial, rural and urban environments were analysed using infrared and Raman spectroscopic methods and the vibrational modes of SO42- ion, OH radical and H2O molecules have been identified and discussed. The symmetric stretching vibrations of the SO42- ion of the compounds give an indication of the distorted structure for the SO4 anion in the compounds, the distortion being more in Zn4Cl2(OH)(4)SO4 center dot 5H(2)O. Due to the presence of strong hydrogen bond network, an unusual lowering of the symmetric stretching mode of SO4 is observed in both the compounds. In NaZn4Cl(OH)(6)SO4 center dot 6H(2)O, medium to weak hydrogen bonding network is present while strong to weak hydrogen bonding is present in Zn4Cl2(OH)(4)SO4 center dot 5H(2)O.
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26. |
- Kuemmerli, Christoph, et al.
(author)
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Impact of enhanced recovery protocols after pancreatoduodenectomy : meta-analysis
- 2022
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In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 256-266
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Journal article (peer-reviewed)abstract
- BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.
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27. |
- Kumar, Nallani Vijay, et al.
(author)
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Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8.
- 2016
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In: Molecular and cellular biology. - 1098-5549. ; 36:6, s. 913-22
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Journal article (peer-reviewed)abstract
- The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.
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28. |
- Nyenswah, TG, et al.
(author)
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Ebola and Its Control in Liberia, 2014-2015
- 2016
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In: Emerging infectious diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6059 .- 1080-6040. ; 22:2, s. 169-177
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Journal article (peer-reviewed)
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32. |
- Pomara, Nunzio, et al.
(author)
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Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression.
- 2021
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In: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 286, s. 275-281
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Journal article (peer-reviewed)abstract
- Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) mechanism contributed to increased neuroinflammation observed in depression.We measured cerebrospinal fluid (CSF) cholinergic markers (AChE and BChE activities) in 28 individuals with longstanding late-life major depression (LLMD) and 19 controls and their relationship to central and peripheral levels of pro-inflammatory cytokines (IL-6 and IL-8). Additionally, we examined if these cholinergic indices were related to CSF markers of microglial activation and neuroinflammation (sTREM2 and complement C3).Compared with controls, LLMD patients had a significant reduction in CSF BChE levels. Lower CSF BChE and AChE activities were associated with lower CSF markers of microglial and neuroinflammation (sTREM2 and C3). In addition, in LLMD patients we found an inverse relationship between peripheral marker of inflammation (plasma IL-6) and CSF BChE and AChE levels.Our results suggest an upregulation of the CAP mechanism in LLMD with an elevation in peripheral markers of inflammation and concomitant reduction in markers of glial activation associated with a higher cholinergic tone. Future studies should confirm these findings in a larger sample including individuals with acute and more severe depressive episodes and across all ages.
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33. |
- Pomara, N., et al.
(author)
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Plasma Amyloid-beta dynamics in late-life major depression: a longitudinal study
- 2022
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Journal article (peer-reviewed)abstract
- Depressed individuals are twice as likely to develop Alzheimer's disease (AD) as compared to controls. Brain amyloid-beta (A beta) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of A beta dynamics and depression. The aim of this study was to test if plasma A beta levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-beta(1-40) (A beta 40) and amyloid-beta(1-42) (A beta 42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the A beta 42/A beta 40 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (p < 0.001). At screening, A beta 42/A beta 40 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression severity at 3 years after adjustment for age, education, cognitive performance, and antidepressants use. This study showed that reduced plasma A beta 42/A beta 40 ratio is consistently associated with LLMD diagnosis and that increased severity of depression at baseline predicted low A beta 42/A beta 40 ratio at 3 years. Future studies are needed to confirm these findings and examine if the consistently lower plasma A beta 42/A beta 40 ratio in LLMD reflects increased brain amyloid deposition, as observed in AD subjects, and an increased risk for progressive cognitive decline and AD.
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34. |
- Szymanski, J. J., et al.
(author)
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A study of the decay mu –> e gamma by the MEGA experiment
- 1996
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In: Proceedings, 9th Meeting, DPF'96, Minneapolis, USA, August 11-15, 1996. Vol. 1, 2.. ; , s. 1450-1452
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Conference paper (peer-reviewed)
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35. |
- Szymanski, J. J., et al.
(author)
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MEGA : A search for the decay mu –> e gamma
- 1994
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In: Intersections between particle and nuclear physics. Proceedings, 5th Conference, St. Petersburg, USA, May 31-June 6, 1994. ; , s. 789-792
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Conference paper (peer-reviewed)
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36. |
- Teo, Kevin, et al.
(author)
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rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis.
- 2021
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In: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:1, s. 20-30
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Journal article (peer-reviewed)abstract
- A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
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