| 1. |
|
|
| 2. |
- Engert, Andreas, et al.
(författare)
-
The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
-
Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
-
Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
|
|
| 3. |
- Badolati, Isabella, et al.
(författare)
-
Staphylococcus aureus-derived factors promote human Th9 cell polarization and enhance a transcriptional program associated with allergic inflammation
- 2023
-
Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 53:3
-
Tidskriftsartikel (refereegranskat)abstract
- T helper (Th) 9 cells, characterized by robust secretion of IL-9, have been increasingly associated with allergic diseases. However, whether and how Th9 cells are modulated by environmental stimuli remains poorly understood. In this study, we show that in vitro exposure of human PBMCs or isolated CD4 T-cells to Staphylococcus (S.) aureus-derived factors, including its toxins, potently enhances Th9 cell frequency and IL-9 secretion. Furthermore, as revealed by RNA sequencing analysis, S. aureus increases the expression of Th9-promoting factors at the transcriptional level, such as FOXO1, miR-155, and TNFRSF4. The addition of retinoic acid (RA) dampens the Th9 responses promoted by S. aureus and substantially changes the transcriptional program induced by this bacterium, while also altering the expression of genes associated with allergic inflammation. Together, our results demonstrate a strong influence of microbial and dietary factors on Th9 cell polarization, which may be important in the context of allergy development and treatment.
|
|
| 4. |
- Davanian, Haleh, et al.
(författare)
-
Ameloblastoma RNA profiling uncovers a distinct non-coding RNA signature
- 2017
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:3, s. 4530-4542
-
Tidskriftsartikel (refereegranskat)abstract
- Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumourgenesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncRNAs accompanied by signalling pathways of cancer, spliceosome, mRNA surveillance and Wnt. Further validation in an independent cohort points out the long non-coding (lncRNAs) and small nucleolar RNA (snoRNAs): LINC340, SNORD116-25, SNORA11, SNORA21, SNORA47 and SNORA65 as a distinct ncRNA signature of ameloblastoma. Importantly, the presence of these ncRNAs was independent of BRAFV600E and SMO-L412F mutations, histology type or tumour location, but was positively correlated with the tumour size. Taken together, this study shows a systematic investigation of ncRNA expression of ameloblastoma, and illuminates new diagnostic and therapeutic targets for this invasive odontogenic tumour.
|
|
| 5. |
- Eissler, Nina, et al.
(författare)
-
Regulation of myeloid cells by activated T cells determines the efficacy of PD-1 blockade
- 2016
-
Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 5:12
-
Tidskriftsartikel (refereegranskat)abstract
- Removal of immuno-suppression has been reported to enhance antitumor immunity primed by checkpoint inhibitors. Although PD-1 blockade failed to control tumor growth in a transgenic murine neuroblastoma model, concurrent inhibition of colony stimulating factor 1 receptor (CSF-1R) by BLZ945 reprogrammed suppressive myeloid cells and significantly enhanced therapeutic effects. Microarray analysis of tumor tissues identified a significant increase of T-cell infiltration guided by myeloid cell-derived chemokines CXCL9, 10, and 11. Blocking the responsible chemokine receptor CXCR3 hampered T-cell infiltration and reduced antitumor efficacy of the combination therapy. Multivariate analysis of 59 immune-cell parameters in tumors and spleens detected the correlation between PD-L1-expressing myeloid cells and tumor burden. In vitro, anti-PD-1 antibody Nivolumab in combination with BLZ945 increased the activation of primary human T and NK cells. Importantly, we revealed a previously uncharacterized pathway, in which T cells secreted M-CSF upon PD-1 blockade, leading to enhanced suppressive capacity of monocytes by upregulation of PD-L1 and purinergic enzymes. In multiple datasets of neuroblastoma patients, gene expression of CD73 correlated strongly with myeloid cell markers CD163 and CSF-1R in neuroblastoma tumors, and associated with worse survival in high-risk patients. Altogether, our data reveal the dual role of activated T cells on myeloid cell functions and provide a rationale for the combination therapy of anti-PD-1 antibody with CSF-1R inhibitor.
|
|
| 6. |
- Hao, Xiaojin, et al.
(författare)
-
Angiogenic effects of sequential release of VEGF-A(165) and PDGF-BB with alginate hydrogels after myocardial infarction
- 2007
-
Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 28, s. 612-612
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A(165) (VEGF-A(165)) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction. Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with I-125-labelled VEGF-A(165) and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A(165), PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice. Results: Alginate gets were capable of delivering VEGF-A(165) and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A(165). Sequential growth factor administration led to a higher density of alpha-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration. Conclusions: The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A(165) and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.
|
|
| 7. |
|
|
| 8. |
- Henriksson, Pontus, et al.
(författare)
-
DNA methylation in infants with low and high body fatness
- 2020
-
Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundBirth weight is determined by the interplay between infant genetics and the intrauterine environment and is associated with several health outcomes in later life. Many studies have reported an association between birth weight and DNA methylation in infants and suggest that altered epigenetics may underlie birthweight-associated health outcomes. However, birth weight is a relatively nonspecific measure of fetal growth and consists of fat mass and fat-free mass which may have different effects on health outcomes which motivates studies of infant body composition and DNA methylation. Here, we combined genome-wide DNA methylation profiling of buccal cells from 47 full-term one-week old infants with accurate measurements of infant fat mass and fat-free mass using air-displacement plethysmography.ResultsNo significant association was found between DNA methylation in infant buccal cells and infant body composition. Moreover, no association between infant DNA methylation and parental body composition or indicators of maternal glucose metabolism were found.ConclusionsDespite accurate measures of body composition, we did not identify any associations between infant body fatness and DNA methylation. These results are consistent with recent studies that generally have identified only weak associations between DNA methylation and birthweight. Although our results should be confirmed by additional larger studies, our findings may suggest that differences in DNA methylation between individuals with low and high body fatness may be established later in childhood.
|
|
| 9. |
- Jiao, Hong, et al.
(författare)
-
Genome wide association study identifies KCNMA1 contributing to human obesity
- 2011
-
Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 4, s. 51-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity. Methods: We performed a GWA analysis in 164 morbidly obese subjects (BMI: body mass index > 40 kg/m(2)) and 163 Swedish subjects (> 45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal P< 0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n = 4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for 14 adults. Results: Potassium channel, calcium activated, large conductance, subfamily M, alpha member (KCNMA1) rs2116830*G and BDNF rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for KCNMA1 rs2116830*G with P = 2.82 x 10(-10) and an odds ratio (OR) based on cases vs controls of 1.26 [95% C. I. 1.12-1.41] and for BDNF rs988712*G with P = 5.2 x 10(-17) and an OR of 1.36 [95% C. I. 1.20-1.55]. KCNMA1 rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (P = 0.0001) and fat cell (P = 0.04) expression of KCNMA1 was increased in obesity. Conclusions: We have identified KCNMA1 as a new susceptibility locus for obesity, and confirmed the association of the BDNF locus at the genome-wide significant level.
|
|
| 10. |
- Just, David, et al.
(författare)
-
Autoantibodies against the C-terminus of Lipopolysaccharide binding protein are elevated in young adults with psychiatric disease
- 2021
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 126
-
Tidskriftsartikel (refereegranskat)abstract
- Growing evidence implies interactions between infections, the immune system and vulnerability for psychiatric disease. This study applies an affinity proteomic-based method to investigate potential disease associated autoantibody signatures in serum from patients from the "Young Adults" section of the Department of General Psychiatry at Uppsala University Hospital (n = 395) and population-based controls (n = 102). We found serum levels of antibodies against Lipopolysaccharide Binding Protein (LBP), a protein that is important for mediating innate immune responses involving the toll-like receptor-4 (TLR-4), to be higher in patients compared to controls (Mann Whitney U-test p = 5.248 x 10(-10)). The patients were divided into three groups based on their relative levels of autoantibodies against LBP. The distribution of autism spectra disorders (p = 2.0 x 10(-4)) and hospital care for an infection as adults (p = 0.036) differed between the anti-LBP groups, with low incidence in the group of patients with the highest levels of anti-LBP who were diagnosed with primarily affective and anxiety disorders. In a sub-group analysis, the controls who screened positive for current or previous psychiatric diagnosis (n = 20) had higher anti-LBP compared to non-psychiatric controls with negative screening for psychiatric disorders (Mann Whitney U-test p = 0.006). Inflammatory markers were found to differ across anti-LBP groups and several pro-inflammatory markers, including IL-1 beta, were low in patients with high anti-LBP and serum LBP levels were lowest in patients with the highest levels of antibodies against LBP (p = 3.5 x 10(-5)). A cell-based model showed that polyclonal rabbit anti-LBP, obtained through purification via the same protein fragment used in the initial autoantibody analysis, could interfere with LBP signaling since addition of anti-LBP to the assay reduced both IL-1 beta and IL-6 release from activated monocytes in response to LBP and LPS (p = 0.0001 and p = 0.02). This novel finding of antibodies against LBP, where high levels were only found in young adults with psychiatric disease, merits further study. Our results suggest that these antibodies may have relevance for TLR4 based immune responses and vulnerability for both infection and psychiatric disorders.
|
|
| 11. |
- Järver, Peter, et al.
(författare)
-
Single-Stranded Nucleic Acids Regulate TLR3/4/7 Activation through Interference with Clathrin-Mediated Endocytosis
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Recognition of nucleic acids by endosomal Toll-like receptors (TLR) is essential to combat pathogens, but requires strict control to limit inflammatory responses. The mechanisms governing this tight regulation are unclear. We found that single-stranded oligonucleotides (ssON) inhibit endocytic pathways used by cargo destined for TLR3/4/7 signaling endosomes. Both ssDNA and ssRNA conferred the endocytic inhibition, it was concentration dependent, and required a certain ssON length. The ssON-mediated inhibition modulated signaling downstream ofTLRs that localized within the affected endosomal pathway. We further show that injection of ssON dampens dsRNA-mediated inflammatory responses in the skin of non-human primates. These studies reveal a regulatory role for extracellular ssON in the endocytic uptake of TLR ligands and provide a mechanistic explanation of their immunomodulation. The identified ssON-mediated interference of endocytosis (SOMIE) is a regulatory process that temporarily dampens TLR3/4/7 signaling, thereby averting excessive immune responses.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Lennox, Robert J., et al.
(författare)
-
A role for lakes in revealing the nature of animal movement using high dimensional telemetry systems
- 2021
-
Ingår i: Movement Ecology. - : BioMed Central. - 2051-3933. ; 9:1
-
Forskningsöversikt (refereegranskat)abstract
- Movement ecology is increasingly relying on experimental approaches and hypothesis testing to reveal how, when, where, why, and which animals move. Movement of megafauna is inherently interesting but many of the fundamental questions of movement ecology can be efficiently tested in study systems with high degrees of control. Lakes can be seen as microcosms for studying ecological processes and the use of high-resolution positioning systems to triangulate exact coordinates of fish, along with sensors that relay information about depth, temperature, acceleration, predation, and more, can be used to answer some of movement ecology's most pressing questions. We describe how key questions in animal movement have been approached and how experiments can be designed to gather information about movement processes to answer questions about the physiological, genetic, and environmental drivers of movement using lakes. We submit that whole lake telemetry studies have a key role to play not only in movement ecology but more broadly in biology as key scientific arenas for knowledge advancement. New hardware for tracking aquatic animals and statistical tools for understanding the processes underlying detection data will continue to advance the potential for revealing the paradigms that govern movement and biological phenomena not just within lakes but in other realms spanning lands and oceans.
|
|
| 15. |
- Lennox, Robert J., et al.
(författare)
-
Electronic tagging and tracking aquatic animals to understand a world increasingly shaped by a changing climate and extreme weather events
- 2024
-
Ingår i: Canadian Journal of Fisheries and Aquatic Sciences. - 0706-652X .- 1205-7533. ; 81:3, s. 326-339
-
Tidskriftsartikel (refereegranskat)abstract
- Despite great promise for understanding the impacts and extent of climate change and extreme weather events on aquatic animals, their species, and ecological communities, it is surprising that electronic tagging and tracking tools, like biotelemetry and biologging, have not been extensively used to understand climate change or develop and evaluate potential interventions that may help adapt to its impacts. In this review, we provide an overview of methodologies and study designs that leverage available electronic tracking tools to investigate aspects of climate change and extreme weather events in aquatic ecosystems. Key interventions to protect aquatic life from the impacts of climate change, including habitat restoration, protected areas, conservation translocations, mitigations against interactive effects of climate change, and simulation of future scenarios, can all be greatly facilitated by using electronic tagging and tracking. We anticipate that adopting animal tracking to identify phenotypes, species, or ecosystems that are vulnerable or resilient to climate change will help in applying management interventions such as fisheries management, habitat restoration, invasive species control, or enhancement measures that prevent extinction and strengthen the resilience of communities against the most damaging effects of climate change. Given the scalability and increasing accessibility of animal tracking tools for researchers, tracking individual organisms will hopefully also facilitate research into effective solutions and interventions against the most extreme and acute impacts on species, populations, and ecosystems.
|
|
| 16. |
- Lennox, Robert J., et al.
(författare)
-
Positioning aquatic animals with acoustic transmitters
- 2023
-
Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 14:10, s. 2514-2530
-
Forskningsöversikt (refereegranskat)abstract
- Geolocating aquatic animals with acoustic tags has been ongoing for decades, relying on the detection of acoustic signals at multiple receivers with known positions to calculate a 2D or 3D position, and ultimately recreate the path of an aquatic animal from detections at fixed stations.This method of underwater geolocation is evolving with new software and hardware options available to help investigators design studies and calculate positions using solvers based predominantly on time-difference-of-arrival and time-of-arrival.We provide an overview of the considerations necessary to implement positioning in aquatic acoustic telemetry studies, including how to design arrays of receivers, test performance, synchronize receiver clocks and calculate positions from the detection data. We additionally present some common positioning algorithms, including both the free open-source solvers and the ‘black-box’ methods provided by some manufacturers for calculating positions.This paper is the first to provide a comprehensive overview of methods and considerations for designing and implementing better positioning studies that will support users, and encourage further knowledge advances in aquatic systems.
|
|
| 17. |
- Oikonomakis, Ioannis, 1977-, et al.
(författare)
-
Altered mRNA Expression Due to Rectal Perforation in a Porcine Model-A Pilot Study
- 2022
-
Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 42:6, s. 2827-2833
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Anastomotic leakage is the most serious and unwelcome complication in rectal surgery. It has a great impact on postoperative morbidity and mortality. In this pilot study, changes of mRNA expression in blood were analyzed in an animal model designed to imitate anastomotic leakage. Materials and Methods: Twelve pigs were randomized into two groups: A sham-operated control group and an experimental group in which iatrogenic rectal perforation was performed. The changes in the mRNA expression at 4 hours after creating the perforation were studied. Microarray analysis was performed using Gene Chip whole porcine genome array. mRNA expression of 19,124 genes was investigated. Results: Significantly increased levels of genes with a fold change greater than 2 were found, including 276 coding for unknown proteins and 48 coding for known proteins. Eleven of those which coded for known proteins were up-regulated with a fold change >4. Conclusion: Eleven known genes were highly up-regulated after rectal perforation. These genes were mainly involved in inflammatory response, intracellular signaling and cell membrane regulation. Their corresponding proteins might potentially be clinical biomarkers of anastomotic leakage and should be evaluated in further clinical studies.
|
|
| 18. |
|
|
| 19. |
- Ostergaard, Mikkel, et al.
(författare)
-
Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis : 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial
- 2023
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 82:10, s. 1286-1295
-
Tidskriftsartikel (refereegranskat)abstract
- Background The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. Methods Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naive early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI <= 2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025). Results Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences. Conclusions Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments.
|
|
| 20. |
- Outomuro, David, et al.
(författare)
-
Preference for supernormal stimuli tends to override initially learned associations for conspicuous prey traits : implications from a laboratory study
- 2020
-
Ingår i: Journal of ethology. - : SPRINGER JAPAN KK. - 0289-0771 .- 1439-5444. ; 38:3, s. 365-371
-
Tidskriftsartikel (refereegranskat)abstract
- How predators select on conspicuous prey traits is not well understood. We used a laboratory setup to investigate the role of learning in predator choice of conspicuous visual traits. We used a generalist predator, the great tit, and coloured wings of males of two species of damselflies as prey. Wing pigmentation differs between the species in colour (green vs. blue) and size (large vs. small). Wing pigmentation is a sexually selected trait that experiences negative selection by avian predators. Inexperienced great tits showed no preference for the colour or the size of wing pigmentation. Great tits were then repeatedly exposed to rewarded wings with either large or small wing patch size. When these experienced birds were exposed to both wing patch sizes for the first time, they tended to prefer the wings with the large patch, irrespective of their previous experience. Our results suggest that the choice of the predator was based on an initial association of the trait to a reward followed by a preference for a supernormal stimulus, probably due to a larger sensory stimulation. We discuss the implications of our laboratory results in the light of previous estimates of damselfly predation risk under field conditions.
|
|
| 21. |
- Richmond, Erinn K., et al.
(författare)
-
A diverse suite of pharmaceuticals contaminates stream and riparian food webs
- 2018
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- A multitude of biologically active pharmaceuticals contaminate surface waters globally, yet their presence in aquatic food webs remain largely unknown. Here, we show that over 60 pharmaceutical compounds can be detected in aquatic invertebrates and riparian spiders in six streams near Melbourne, Australia. Similar concentrations in aquatic invertebrate larvae and riparian predators suggest direct trophic transfer via emerging adult insects to riparian predators that consume them. As representative vertebrate predators feeding on aquatic invertebrates, platypus and brown trout could consume some drug classes such as antidepressants at as much as one-half of a recommended therapeutic dose for humans based on their estimated prey consumption rates, yet the consequences for fish and wildlife of this chronic exposure are unknown. Overall, this work highlights the potential exposure of aquatic and riparian biota to a diverse array of pharmaceuticals, resulting in exposures to some drugs that are comparable to human dosages.
|
|
| 22. |
- Shupliakov, O, et al.
(författare)
-
Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions
- 1997
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 276:5310, s. 259-263
-
Tidskriftsartikel (refereegranskat)abstract
- The proline-rich COOH-terminal region of dynamin binds various Src homology 3 (SH3) domain–containing proteins, but the physiological role of these interactions is unknown. In living nerve terminals, the function of the interaction with SH3 domains was examined. Amphiphysin contains an SH3 domain and is a major dynamin binding partner at the synapse. Microinjection of amphiphysin’s SH3 domain or of a dynamin peptide containing the SH3 binding site inhibited synaptic vesicle endocytosis at the stage of invaginated clathrin-coated pits, which resulted in an activity-dependent distortion of the synaptic architecture and a depression of transmitter release. These findings demonstrate that SH3-mediated interactions are required for dynamin function and support an essential role of clathrin-mediated endocytosis in synaptic vesicle recycling.
|
|
| 23. |
- Sigmund, Gabriel, et al.
(författare)
-
Broaden chemicals scope in biodiversity targets
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 376:6599, s. 1279-1280
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 24. |
- Stenegren, Marcus, 1986-, et al.
(författare)
-
Insights on symbiotic diatom diazotroph associations in the South China Sea by targeted microarray analysis of three symbiont strains
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Three heterocystous cyanobacterial strains (two Richelia intracellularis: RintHH01, RintRC01, Calothrix rhizosoleniae: CalSC01) are known to form highly specific, intimate associations with several lineages of diatoms. Collectively these symbioses are unique since the cellular location varies from internal, partially integrated, and fully external; hence the immediate environment of the symbiont differs. We investigated the environmental gene expression levels of the three strains using a targeted mRNA microarray comprised of 748 genes on environmental samples collected in the South China Sea. Approximately half of the total genes (47%, 354 of the 748 genes) were expressed above background. The most highly transcribed genes were involved in photosynthesis, N2 fixation and potassium homeostasis, and strain differences were identifiable. The most important environmental parameters on the symbiont gene expression levels were fluorescence, temperature and beam transmission. However, salinity and oxygen impacted gene expression levels of one symbiont strain, RintHH01 differently (positively), possibly due to its different cellular location. Our results suggest that differences in gene expression patterns and environmental conditions influence the three closely related symbiont strains, and are likely related to their cellular location in their respective host diatoms.
|
|
| 25. |
- Stratoulias, Vassilis, et al.
(författare)
-
ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
- 2023
-
Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 26:6, s. 1008-1020
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1- microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.
|
|
| 26. |
- Tyagi, Anu, et al.
(författare)
-
SWI/SNF Associates with Nascent Pre-mRNPs and Regulates Alternative Pre mRNA Processing
- 2009
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:5
-
Tidskriftsartikel (refereegranskat)abstract
- The SWI/SNF chromatin remodeling complexes regulate the transcription of many genes by remodeling nucleosomes at promoter regions. In Drosophila, SWI/SNF plays an important role in ecdysone-dependent transcription regulation. Studies in human cells suggest that Brahma (Brm), the ATPase subunit of SWI/SNF, regulates alternative pre-mRNA splicing by modulating transcription elongation rates. We describe, here, experiments that study the association of Brm with transcribed genes in Chironomus tentans and Drosophila melanogaster, the purpose of which was to further elucidate the mechanisms by which Brm regulates pre-mRNA processing. We show that Brm becomes incorporated into nascent Balbiani ring pre-mRNPs co-transcriptionally and that the human Brm and Brg1 proteins are associated with RNPs. We have analyzed the expression profiles of D. melanogaster S2 cells in which the levels of individual SWI/SNF subunits have been reduced by RNA interference, and we show that depletion of SWI/SNF core subunits changes the relative abundance of alternative transcripts from a subset of genes. This observation, and the fact that a fraction of Brm is not associated with chromatin but with nascent pre-mRNPs, suggest that SWI/SNF affects pre-mRNA processing by acting at the RNA level. Ontology enrichment tests indicate that the genes that are regulated post-transcriptionally by SWI/SNF are mostly enzymes and transcription factors that regulate postembryonic developmental processes. In summary, the data suggest that SWI/SNF becomes incorporated into nascent pre-mRNPs and acts post-transcriptionally to regulate not only the amount of mRNA synthesized from a given promoter but also the type of alternative transcript produced.
|
|
| 27. |
- Waldholm, Johan, et al.
(författare)
-
SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in Drosophila melanogaster
- 2011
-
Ingår i: BMC Molecular Biology. - : Springer Science and Business Media LLC. - 1471-2199. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA.Results: We have investigated whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of depleting individual SWI/SNF subunits on pre-mRNA processing throughout the genome, and we have identified a subset of transcripts that are affected by depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion of different subunits targets a subset of common transcripts suggests that the SWI/SNF complex is responsible for the effects observed on pre-mRNA processing when knocking down Brm. We have also depleted Brm in larvae and we have shown that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo.Conclusions: We have shown that SWI/SNF can modulate alternative pre-mRNA processing, not only in cultured cells but also in vivo. The effect is restricted to and specific for a subset of transcripts. Our results provide novel insights into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic diversity in higher eukaryotes.
|
|
| 28. |
- Xue-Franzen, Yongtao, et al.
(författare)
-
Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles
- 2010
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Gcn5 is a transcriptional coactivator with histone cetyltransferase activity that is conserved with regard to structure as ell as its histone substrates throughout the eukaryotes. Gene egulatory networks within cells are thought to be evolutionarily iverged. The use of evolutionarily divergent yeast species, such as S. erevisiae and S. pombe, which can be studied under similar nvironmental conditions, provides an opportunity to examine the nterface between conserved regulatory components and their cellular pplications in different organisms. esults: We show that Gcn5 is important for a common set of stress esponses in evolutionarily diverged yeast species and that the activity f the conserved histone acetyltransferase domain is required. We define group of KCl stress response genes in S. cerevisiae that are pecifically dependent on Gcn5. Gcn5 is localised to many Gcn5-dependent enes including Gcn5 repressed targets such as FLO8. Gcn5 regulates ivergent sets of KCl responsive genes in S. cerevisiae and S. pombe. enome-wide localization studies showed a tendency for redistribution of cn5 during KCl stress adaptation in S. cerevisiae from short genes to he transcribed regions of long genes. An analogous redistribution was ot observed in S. pombe. onclusions: Gcn5 is required for the regulation of divergent sets of Cl stress-response genes in S. cerevisiae and S. pombe even though it s required a common group of stress responses, including the response o KCl. Genes that are physically associated with Gcn5 require its ctivity for their repression or activation during stress adaptation, roviding support for a role of Gcn5 as a corepressor as well as a oactivator. The tendency of Gcn5 to re-localise to the transcribed egions of long genes during KCl stress adaptation suggests that Gcn5 lays a specific role in the expression of long genes under adaptive onditions, perhaps by regulating transcriptional elongation as has been een for Gcn5 in S. pombe. Interestingly an analogous redistribution of cn5 is not seen in S. pombe. The study thus provides important new nsights in relation to why coregulators like Gcn5 are required for the orrect expression of some genes but not others.
|
|
| 29. |
- Åhlén, David, 1988-, et al.
(författare)
-
Wetland productivity determines trade-off between biodiversity support and greenhouse gas production
- 2023
-
Ingår i: Ecology and Evolution. - 2045-7758. ; 13:10
-
Tidskriftsartikel (refereegranskat)abstract
- Establishing wetlands for nutrient capture and biodiversity support may introduce trade-offs between environmentally beneficial functions and detrimental greenhouse gas emissions. Investigating the interaction of nutrient capture, primary production, greenhouse gas production and biodiversity support is imperative to understanding the overall function of wetlands and determining possible beneficial synergistic effects and trade-offs. Here, we present temporally replicated data from 17 wetlands in hemi-boreal Sweden. We explored the relationship between nutrient load, primary producing algae, production of methane and nitrous oxide, and emergence rates of chironomids to determine what factors affected each and how they related to each other. Chironomid emergence rates correlated positively with methane production and negatively with nitrous oxide production, where water temperature was the main driving factor. Increasing nutrient loads reduced methanogenesis through elevated nitrogen concentrations, while simultaneously enhancing nitrous oxide production. Nutrient loads only indirectly increased chironomid emergence rates through increased chlorophyll-a concentration, via increased phosphorus concentrations, with certain taxa and food preference functional groups benefitting from increased chlorophyll-a concentrations. However, water temperature seemed to be the main driving factor for chironomid emergence rates, community composition and diversity, as well as for greenhouse gas production. These findings increase our understanding of the governing relationships between biodiversity support and greenhouse gas production, and should inform future management when constructing wetlands.
|
|
