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- Sakaguchi, M., et al.
(author)
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FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
- 2019
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function.
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- Attermeyer, Katrin, et al.
(author)
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Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km(2)) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets.
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- Gottardo, A., et al.
(author)
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Isomers in Neutron-rich Lead Isotopes Populated via the Fragmentation of 238U at 1 GeV A
- 2011
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 312
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Journal article (peer-reviewed)abstract
- Neutron-rich nuclei beyond N = 126 in the lead region were populated by fragmenting a 238U beam at 1 GeV A on a Be target and then separated by the Fragment Separator (FRS) at GSI. Their isomeric decays were observed, enabling study of the shell structure of neutron-rich nuclei around the Z=82 shell closure. Some preliminary results are reported in this paper.
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| 7. |
- Berg, E, et al.
(author)
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Chronic Prostatitis/Chronic Pelvic Pain Syndrome Leads to Impaired Semen Parameters, Increased Sperm DNA Fragmentation and Unfavorable Changes of Sperm Protamine mRNA Ratio
- 2021
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:15
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Journal article (peer-reviewed)abstract
- Background: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters. Methods: Sperm DNA fragmentation measured by sperm chromatin structure assay (SCSA) and protamine 1 to protamine 2 mRNA ratio assessed by RT-qPCR were analyzed along with conventional ejaculate parameters and inflammatory markers in 41 CP/CPPS patients and 22 healthy volunteers. Results: We found significant differences between the groups concerning multiple conventional ejaculate parameters. A significant increase in sperm DNA fragmentation was shown in CP/CPPS patients with association to other sperm parameters. The majority of CP/CPPS patients exhibited protamine mRNA ratios out of the range of regular fertility. Conclusions: This is a pioneering study with a strong practical orientation revealing that CP/CPPS leads to increased sperm DNA damage and changes in sperm protamine levels, emphasizing an unfavorable impact of CP/CPPS on fertility.
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| 9. |
- Cazzaniga, Marina E., et al.
(author)
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Metastatic or locally advanced breast cancer patients : towards an expert consensus on nab-paclitaxel treatment in HER2-negative tumoursthe MACBETH project
- 2019
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 83:2, s. 301-318
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Journal article (peer-reviewed)abstract
- Introduction: Despite the large use of nab-paclitaxel as a treatment option in metastatic breast cancer (MBC) across different countries, no definitive data are available in particular clinical situations.Areas covered: Efficacy, safety and schedule issues concerning available literature on nab-paclitaxel in advanced breast cancer and in specific subgroups of patients have been discussed and voted during an International Expert Meeting. Ten expert specialists in oncology, with extensive clinical experience on Nab-P and publications in the field of MBC have been identified. Six scientific areas of interest have been covered, generating 13 specific Statements for Nab-P, after literature review. For efficacy issues, a summary of research quality was performed adopting the GRADE algorithm for evidence scoring. The panel members were invited to express their opinion on the statements, in case of disagreement all the controversial opinions and the relative motivations have been made public.Expert opinion: Consensus was reached in 30.8% of the Nab-P statements, mainly those regarding safety issues, whereas ones regarding efficacy and schedule still remain controversial areas, requiring further data originated by the literature.
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| 12. |
- Elser, JJ, et al.
(author)
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Shifts in lake N:P stoichiometry and nutrient limitation driven by atmospheric nitrogen deposition
- 2009
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326, s. 835-837
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Journal article (peer-reviewed)abstract
- Human activities have more than doubled the amount of nitrogen (N) circulating in the biosphere. One major pathway of this anthropogenic N input into ecosystems has been increased regional deposition from the atmosphere. Here we show that atmospheric N deposition increased the stoichiometric ratio of N and phosphorus (P) in lakes in Norway, Sweden, and Colorado, United States, and, as a result, patterns of ecological nutrient limitation were shifted. Under low N deposition, phytoplankton growth is generally N-limited; however, in high–N deposition lakes, phytoplankton growth is consistently P-limited. Continued anthropogenic amplification of the global N cycle will further alter ecological processes, such as biogeochemical cycling, trophic dynamics, and biological diversity, in the world’s lakes, even in lakes far from direct human disturbance.
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| 17. |
- Neely, K E, et al.
(author)
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Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays
- 1999
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In: Molecular Cell. - 1097-2765 .- 1097-4164. ; 4:4, s. 649-655
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Journal article (peer-reviewed)abstract
- The yeast SWI/SNF complex is required for the transcription of several yeast genes and has been shown to alter nucleosome structure in an ATP-dependent reaction. In this study, we show that the complex stimulated in vitro transcription from nucleosome templates in an activation domain-dependent manner. Transcription stimulation by SWI/SNF required an activation domain with which it directly interacts. The acidic activation domains of VP16, Gcn4, Swi5, and Hap4 interacted directly with the purified SWI/SNF complex and with the SWI/SNF complex in whole-cell extracts. The similarity of activation domain interactions and transcriptional stimulation between SWI/SNF and the SAGA histone acetyltransferase complex may account for their apparent overlapping functions in vivo.
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| 18. |
- Steger, Kristin, et al.
(author)
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Comparative study on bacterial carbon sources in lake sediments : the role of methanotrophy
- 2015
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In: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 76:1, s. 39-47
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Journal article (peer-reviewed)abstract
- Methane-derived carbon can be important in both benthic and pelagic food webs. Either generated in the anaerobic layers of the sediment or in the anaerobic hypolimnion of stratified eutrophic lakes, methane is an excellent carbon source for aerobic methanotrophic bacteria. The very negative methane δ13C-signal in the methanotrophic biomass provides an excellent opportunity to trace the use of methane-derived carbon in food webs. We studied carbon sources of benthic bacteria in a range of Swedish lakes with different inputs of terrestrial organic carbon and indigenous primary production. We analyzed the 13C:12C ratios in phospholipid-derived fatty acids, which serve as biomarkers for specific groups of Bacteria. We demonstrate that methane is an important carbon source for sediment bacteria, not only for the methanotrophic community but also for the non-methanotrophic heterotrophic bacteria. This most likely indirect utilization of isotopically highly depleted methane masks the stable isotope signatures for terrestrial input and local primary production in the heterotrophic bacterial community.
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| 19. |
- Steger, Kristin, et al.
(author)
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Development of compost maturity and Actinobacteria populations during full-scale composting of organic household waste
- 2007
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In: Journal of Applied Microbiology. - : Oxford University Press (OUP). - 1364-5072 .- 1365-2672. ; 103:2, s. 487-498
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Journal article (peer-reviewed)abstract
- AIMS: This study investigates changes in microbiological and physicochemical parameters during large-scale, thermophilic composting of a single batch of municipal organic waste. The inter-relationships between the microbial biomass and community structure as well as several physicochemical parameters and estimates of maturation were evaluated. METHODS AND RESULTS: Analyses of signature fatty acids with the phospholipid fatty acid and ester-linked methods showed that the total microbial biomass was highest during the early thermophilic phase. The contribution of signature 10Me fatty acids from Actinobacteria indicated a relatively constant proportion around 10% of the microbial community. However, analyses of the Actinobacteria species composition with a PCR-denaturing gradient gel electrophoresis approach targeting 16S rRNA genes demonstrated clear shifts in the community structure. CONCLUSIONS: This study demonstrates that compost quality, particularly maturity, is linked to the composition of the microbial community structure, but further studies in other full-scale systems are needed to validate the generality of these findings. SIGNIFICANCE AND IMPACT OF THE STUDY: The combination of signature lipid and nucleic acid-based analyses greatly expands the specificity and the scope for assessing the microbial community composition in composts. The results presented in this study give new information on how the development of the compost microbial community is connected to curing and maturation in the later stages of composting, and emphasizes the role of Actinobacteria in this respect.
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| 20. |
- Tutt, A. N. J., et al.
(author)
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Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer
- 2021
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In: New England Journal of Medicine. - 0028-4793. ; 384:25, s. 2394-2405
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Journal article (peer-reviewed)abstract
- BACKGROUND Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.
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