| 1. |
- Jardin, Fabrice, et al.
(författare)
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Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma.
- 2016
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 91:9, s. 923-30
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Tidskriftsartikel (refereegranskat)abstract
- Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.
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| 2. |
- Larochelle, Jean, et al.
(författare)
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Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec.
- 2012
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Ingår i: Molecular genetics and metabolism. - : Elsevier BV. - 1096-7206 .- 1096-7192. ; 107:1-2, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency, MIM 276700) can cause severe hepatic, renal and peripheral nerve damage. In Québec, HT1 is frequent and neonatal HT1 screening is practiced. Nitisinone (NTBC, Orfadin ®) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone and has been offered to HT1 patients in Québec since 1994.
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| 3. |
- Ahmadi Afzadi, Masoud, et al.
(författare)
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Genome-wide expression analysis suggests a role for jasmonates in the resistance to blue mold in apple
- 2018
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Ingår i: Plant growth regulation (Print). - : Springer Science and Business Media LLC. - 0167-6903 .- 1573-5087. ; 85:3, s. 375-387
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Tidskriftsartikel (refereegranskat)abstract
- Blue mold, caused by the necrotrophic fungal pathogen Penicillium expansum, causes serious postharvest losses in apple, and threatens human health through production of the potent mycotoxin patulin. Recent studies indicate a quantitative control of resistance against this disease in apple cultivars. A whole genome apple microarray covering 60k transcripts was used to identify gene(s) that appear to be differentially regulated between resistant and susceptible cultivars in P. expansum-infected fruits. A number of potential candidates was encountered among defense- and oxidative stress-related genes, cell wall modification and lignification genes, and genes related to localization and transport. Induction of one cell wall-related gene and three genes involved in the 'down-stream' flavonoid biosynthesis pathway, demonstrates the fundamental role of the cell wall as an important barrier, and suggests that fruit flavonoids are involved in the resistance to blue mold. Moreover, exogenous application of the plant hormone methyl jasmonate (MeJA) reduced the symptoms resulting from inoculating apples with P. expansum. This is the first report linking MeJA and activation of cell wall and flavonoid pathway genes to resistance against blue mold in a study comparing different cultivars of domesticated apple. Our results provide an initial categorization of genes that are potentially involved in the resistance mechanism, and should be useful for developing tools for gene marker-assisted breeding of apple cultivars with an improved resistance to blue mold.
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| 4. |
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| 5. |
- Do Rego, Jean-Luc, et al.
(författare)
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Steroid biosynthesis within the frog brain : a model of neuroendocrine regulation
- 2009
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1163, s. 83-92
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Tidskriftsartikel (refereegranskat)abstract
- There is now clear evidence that the brain, similar to the adrenal gland, gonads, and placenta, is a steroidogenic organ. Notably in the frog brain, the presence of various steroidogenic enzymes has been detected by immunohistochemistry in specific populations of neurons and/or glial cells. These steroidogenic enzymes are biologically active, as shown by the ability of brain tissue explants to convert [(3)H]pregnenolone into various radiolabeled steroids. The frog brain has also been extensively used as a model to study the mechanism of regulation of neurosteroidogenesis by neurotransmitters and neuropeptides. It has been demonstrated that the biosynthesis of neurosteroids is inhibited by gamma-aminobutyric acid (GABA), acting through GABA(A) receptors, and neuropeptide Y, acting through Y1 receptors, and is stimulated by the octadecaneuropeptide (ODN), acting through central-type benzodiazepine receptors, triakontatetraneuropeptide (TTN), acting through peripheral-type benzodiazepine receptors, and vasotocin, acting through V1a-like receptors. These data indicate that some of the neurophysiological effects of neurotransmitters and neuropeptides may be mediated through modulation of neurosteroid biosynthesis.
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| 8. |
- Mobasheri, Ali, et al.
(författare)
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Osteoarthritis Research Society International (OARSI) : Past, present and future
- 2021
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:2
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Forskningsöversikt (refereegranskat)abstract
- We provide a detailed account of the origin and establishment of the Osteoarthritis Research Society International (OARSI) and celebrate its history from inception to the current day. We discuss the mission, vision and strategic objectives of OARSI and how these have developed and evolved over the last 3 decades. We celebrate the achievements of the society as we approach its 30th birthday, honor the entire presidential line and respectfully pay tribute to the past presidents who are no longer with us. We reflect on the strong foundations of our society, OARSI's efforts to disseminate understanding of the health, disability and economic burdens of osteoarthritis (OA) to policymakers, and the exciting initiatives to make the society inclusive and international. We thank our corporate and industrial sponsors, who have supported us over many years, without whom our annual congresses would not have been possible. We celebrate our longstanding strategic partnership with our publisher, Elsevier, and the successful launch of our new journal Osteoarthritis and Cartilage Open, the most significant new development in our dissemination toolbox. For the first time in the history of the organization, our annual congress was cancelled in April 2020 and the 2021 meeting will be virtual. Despite the numerous challenges posed by the ongoing COVID-19 pandemic and the need to adapt quickly to a rapidly changing landscape, we must remain optimistic about the future. We will take advantage of new exciting opportunities to advance our mission and vision to enhance the quality of life of persons with OA.
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| 9. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 10. |
- Tang, Yiling, et al.
(författare)
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Physical Literacy for Communities (PL4C): physical literacy, physical activity and associations with wellbeing
- 2023
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Ingår i: BMC Public Health. - 1471-2458. ; 23:1, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Background Physical literacy (PL) is considered an important determinant of children’s physical activity through which health benefits may be derived. The purpose of this study is to describe a sample of Canadian children’s base‑line levels of PL and movement behaviors, and explore whether the associations between PL and their mental well-being, if any, are mediated by moderate‑to‑vigorous physical activity (MVPA). Methods All grade two children in 14 elementary schools in the West Vancouver School District, Canada were invited to participate in a two‑year longitudinal project. PL was assessed through PLAYfun and PLAYself tools. Physical activity was measured by wrist‑worn accelerometers (GT3X + BT) for seven days. Children’s mental well‑being was assessed using the Strengths and Difficulties Questionnaire (SDQ). A score of total difficulties was aggregated for internalizing and externalizing problems. Results A total of 355 children aged 7–9 (183 boys, 166 girls, 6 non‑binary) participated with 258 children providing valid accelerometer data. Children exhibited an average of 111.1 min of MVPA per day, with 97.3% meeting the physical activity guidelines. Approximately 43% (108/250) of participants were meeting the Canadian 24‑h movement guidelines. Children were at an ‘emerging’ level of overall physical competence (45.8 ± 5.6) and reported a mean score of 68.9 (SD = 12.3) for self‑perceived PL, with no significant differences between boys and girls. PL was significantly associated with MVPA (r = .27) and all SDQ variables (rs = ‑.26—.13) except for externalizing problems. Mediation analyses showed PL was negatively associated with internalizing problems and total difficulties when the association with MVPA was considered. However, the mediating role of MVPA was found only between PL and internalizing problems, β = ‑.06, 95%CI [‑.12, ‑.01]. Conclusions Although most of our sample was physically active and showed higher adherence to 24‑H movement guidelines than comparable population data, the motor competence and self‑perceived PL of our sample were similar to those of previous studies. PL has an independent association with children’s internalizing problems and total difficulties. Ongoing assessment will investigate the relationships between PL and children’s mental health from a longitudinal perspective.
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