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- Saarikangas, J, et al.
(författare)
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Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia
- 2011
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 124:8Pt 8, s. 1245-1255
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Tidskriftsartikel (refereegranskat)abstract
- MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
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- Hyttinen, V, et al.
(författare)
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Incident Use of a Potentially Inappropriate Medication and Hip Fracture in Community-Dwelling Older Persons With Alzheimer's Disease
- 2017
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Ingår i: The Annals of pharmacotherapy. - : SAGE Publications. - 1542-6270 .- 1060-0280. ; 51:9, s. 725-734
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Tidskriftsartikel (refereegranskat)abstract
- Background: Potentially inappropriate medications (PIMs) increase the risk of adverse drug reactions and events and have been associated with greater health care service use, such as an increased risk of hospitalization. Objective: The aim of this study is to evaluate the association between PIM use and hip fractures in a nationwide cohort of community-dwelling persons ≥65 years old with Alzheimer’s disease (AD). Methods: The study, which is based on the Finnish nationwide MEDALZ cohort, included all persons diagnosed with AD between 2005 and 2011 (n = 70 718). After a 1-year washout period for PIM use and exclusion of persons with previous hip fracture before AD diagnosis or those who had been hospitalized, we included 47 850 persons ≥65 years old with AD. PIM use was identified using Finnish criteria. Associations between PIM use and hip fracture were analyzed with Cox proportional hazards regression. Results: Of the study population, 12.3% (n = 5895) initiated PIMs during the follow-up (maximum follow-up 2921 days and total number of person-years 139 538.7). Of those, 103 (1.7%) persons had hip fractures during the PIM use period. The results suggest that PIM use was only associated with an increased risk of hip fracture with incident PIM use (adjusted hazard ratio = 1.31; 95% CI = 1.06-1.63; P = 0.014). Conclusions: PIM use is associated with increased risk of hip fracture when a person uses PIMs for the first time. However, the association between PIM use and hip fracture should be investigated more comprehensively in future studies.
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- Kaasinen, E, et al.
(författare)
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Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
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Tidskriftsartikel (refereegranskat)abstract
- Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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- Palin, K, et al.
(författare)
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Contribution of allelic imbalance to colorectal cancer
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3664-
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Tidskriftsartikel (refereegranskat)abstract
- Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
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- Ahokas, Essi, et al.
(författare)
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Menstruation has no effect on heart rate variability and subjective sleep quality of physically active women
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION:Subjective sleep quality may decrease during menstruation, although the duration and composition of sleep remains relatively stable across the menstrual cycle (MC) (1). Recording heart rate variability (HRV) is a tool to monitor the autonomic nervous system and recovery of the body. Meta-analytical data has not revealed significant changes in HRV from the early follicular phase (menses) to the mid-follicular phase (2). However, reduced HRV-values were observed during menses compared to follicular phase in women with pain during menses (dysmenorrhea) (3). Only a few studies have examined effects of the MC on nocturnal HRV. The aim of this study was to investigate how menses and associated pain affects nocturnal HRV and subjective sleep quality.METHODS:Participants included 14 healthy, physically active women, who did not use hormonal contraception. During one MC, participants completed a diary of sleep, MC and related symptoms. HRV was registered every night (Bodyguard 2, Firstbeat Technologies Ltd., Finland). HRV-data (RMSSD and LF/HF-ratio) were analyzed for two nights after a blood sample and over a four-hour period beginning 30 min after bedtime. Only the menses (M) and mid-follicular phases (FP) are used in this study. Blood samples (estradiol, E2, and progesterone, P4) were collected during M (day 2-3 of the MC) and FP (day 7-10) to ensure normal hormonal function associated with the MC (4).RESULTS:E2 was higher (p=0.012) during FP (267±150 pmol/L) compared to M (143±88 pmol/L), but P4 remained stable (p=0.103). Mean heart rate (HRmean) was higher during M (54±8 beats/min) compared to FP (52±7 beats/min, p=0.022). However, HRV-variables did not differ between M and FP (RMSSD: 76.7±34.5 to 77.3±27.0 ms, p=0.872; LF/HF: 1.416±1.380 to 1.273±0.769, p=0.826). Subjectively-assessed sleep quality remained unchanged between M and FP (p=0.349). The change in RMSSD and HRmean between M and FP did not differ (RMSSD: p=0.728; HRmean: p=0.149) between participants with and without menstrual pains.CONCLUSION:Menses has no effect on nocturnal HRV and subjective sleep quality of physically active women, though the higher nocturnal HRmean during M may indicate decreased recovery during menses.REFERENCES:1. Driver, H.S., Werth, E., et al. The Menstrual Cycle Effects on Sleep. Sleep Med Clin 2008, 3:1–11.2. Schmalenberger, K.M., Eisenlohr-Moul, T.M., et al. A Systematic Review and Meta-Analysis of Within-Person Changes in Cardiac Vagal Activity across the Menstrual Cycle: Implications for Female Health and Future Studies. J Clin Med 2019, 8:1946.3. Jayamala, A.K., Preethi, B.L., et al. Comparative Analysis of Heart Rate Variability During Different Phases of Menstrual Cycle in Eumenorrhea & Dysmenorrhea Subjects. Exp Clin Physiol Biochem 2017, 1.4. Elliot-Sale, K.J., Minahan, C.L., et al. Methodological Considerations for Studies in Sport and Exercise Science with Women as Participants: A Working Guide for Standards of Practice for Research on Women. Sports Med 2021, 51:843–861.
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| 35. |
- Ahola, Virpi, et al.
(författare)
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The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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| 37. |
- Andrews, B. J., et al.
(författare)
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Quantitative human cell encyclopedia
- 2016
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 9:443
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Tidskriftsartikel (refereegranskat)abstract
- Scientists gathered to discuss the necessity, feasibility, and challenges of generating a quantitative catalog of the components in human cells that is essential for our understanding of human physiology in health and disease and to support future breakthroughs in treating diseases. This report summarizes the discussion that emerged at the Human Quantitative Dynamics Workshop held in Bethesda, MD, USA, in December 2015.
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- Brett, Michael T., et al.
(författare)
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How important are terrestrial organic carbon inputs for secondary production in freshwater ecosystems?
- 2017
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Ingår i: Freshwater Biology. - : WILEY. - 0046-5070 .- 1365-2427. ; 62:5, s. 833-853
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Forskningsöversikt (refereegranskat)abstract
- 1. Many freshwater systems receive substantial inputs of terrestrial organic matter. Terrestrially derived dissolved organic carbon (t-DOC) inputs can modify light availability, the spatial distribution of primary production, heat, and oxygen in aquatic systems, as well as inorganic nutrient bioavailability. It is also well-established that some terrestrial inputs (such as invertebrates and fruits) provide high-quality food resources for consumers in some systems. 2. In small to moderate-sized streams, leaf litter inputs average approximately three times greater than the autochthonous production. Conversely, in oligo/mesotrophic lakes algal production is typically five times greater than the available flux of allochthonous basal resources. 3. Terrestrial particulate organic carbon (t-POC) inputs to lakes and rivers are comprised of 80%-90% biochemically recalcitrant lignocellulose, which is highly resistant to enzymatic breakdown by animal consumers. Further, t-POC and heterotrophic bacteria lack essential biochemical compounds that are critical for rapid growth and reproduction in aquatic invertebrates and fishes. Several studies have directly shown that these resources have very low food quality for herbivorous zooplankton and benthic invertebrates 4. Much of the nitrogen assimilated by stream consumers is probably of algal origin, even in systems where there appears to be a significant terrestrial carbon contribution. Amino acid stable isotope analyses for large river food webs indicate that most upper trophic level essential amino acids are derived from algae. Similarly, profiles of essential fatty acids in consumers show a strong dependence on the algal food resources. 5. Primary production to respiration ratios are not a meaningful index to assess consumer allochthony because respiration represents an oxidised carbon flux that cannot be utilised by animal consumers. Rather, the relative importance of allochthonous subsidies for upper trophic level production should be addressed by considering the rates at which terrestrial and autochthonous resources are consumed and the growth efficiency supported by this food. 6. Ultimately, the biochemical composition of a particular basal resource, and not just its quantity or origin, determines how readily this material is incorporated into upper trophic level consumers. Because of its highly favourable biochemical composition and greater availability, we conclude that microalgal production supports most animal production in freshwater ecosystems.
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