Our objective was to identify the biological response and the cross-talk between liver and mammary tissue after intramammary infection (IMI) with Escherichia coli (E. coli) using RNAseq technology. ...Sixteen cows were inoculated with live E. coli into one mammary quarter at ~4-6 weeks in lactation. For all cows, biopsies were performed at -144, 12 and 24 h relative to IMI in liver and at 24 h post-IMI in infected and non-infected (control) mammary quarters. For a subset of cows (n = 6), RNA was extracted from both liver and mammary tissue and sequenced using a 100 bp paired-end approach. Ingenuity Pathway Analysis and the Dynamic Impact Approach analysis of differentially expressed genes (overall effect False Discovery Rate≤0.05) indicated that IMI induced an overall activation of inflammation at 12 h post-IMI and a strong inhibition of metabolism, especially related to lipid, glucose, and xenobiotics at 24 h post-IMI in liver. The data indicated in mammary tissue an overall induction of inflammatory response with little effect on metabolism at 24 h post-IMI. We identified a large number of up-stream regulators potentially involved in the response to IMI in both tissues but a relatively small core network of transcription factors controlling the response to IMI for liver whereas a large network in mammary tissue. Transcriptomic results in liver and mammary tissue were supported by changes in inflammatory and metabolic mediators in blood and milk. The analysis of potential cross-talk between the two tissues during IMI uncovered a large communication from the mammary tissue to the liver to coordinate the inflammatory response but a relatively small communication from the liver to the mammary tissue. Our results indicate a strong induction of the inflammatory response in mammary tissue and impairment of liver metabolism 24h post-IMI partly driven by the signaling from infected mammary tissue.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pathogenic germline mutations in BRCA1 or BRCA2 are detected in less than one third of families with a strong history of breast cancer. It is therefore expected that mutations still remain undetected ...by currently used screening methods. In addition, a growing number of BRCA1/2 sequence variants of unclear pathogen significance are found in the families, constituting an increasing clinical challenge. New methods are therefore needed to improve the detection rate and aid the interpretation of the clinically uncertain variants. In this study we analyzed a series of 33 BRCA1, 22 BRCA2, and 128 sporadic tumors by RNA profiling to investigate the classification potential of RNA profiles to predict BRCA1/2 mutation status. We found that breast tumors from BRCA1 and BRCA2 mutation carriers display characteristic RNA expression patterns, allowing them to be distinguished from sporadic tumors. The majority of BRCA1 tumors were basal-like while BRCA2 tumors were mainly luminal B. Using RNA profiles, we were able to distinguish BRCA1 tumors from sporadic tumors among basal-like tumors with 83% accuracy and BRCA2 from sporadic tumors among luminal B tumors with 89% accuracy. Furthermore, subtype-specific BRCA1/2 gene signatures were successfully validated in two independent data sets with high accuracies. Although additional validation studies are required, indication of BRCA1/2 involvement ("BRCAness") by RNA profiling could potentially be valuable as a tool for distinguishing pathogenic mutations from benign variants, for identification of undetected mutation carriers, and for selecting patients sensitive to new therapeutics such as PARP inhibitors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The European Academy of Wind Energy (eawe), representing universities and institutes with a significant wind energy programme in 14 countries, has discussed the long-term research challenges in wind ...energy. In contrast to research agendas addressing short- to medium-term research activities, this eawe document takes a longer-term perspective, addressing the scientific knowledge base that is required to develop wind energy beyond the applications of today and tomorrow. In other words, this long-term research agenda is driven by problems and curiosity, addressing basic research and fundamental knowledge in 11 research areas, ranging from physics and design to environmental and societal aspects. Because of the very nature of this initiative, this document does not intend to be permanent or complete. It shows the vision of the experts of the eawe, but other views may be possible. We sincerely hope that it will spur an even more intensive discussion worldwide within the wind energy community.
Abstract
Background
People with multiple sclerosis (MS) experience a wide range of unpredictable and variable symptoms. The symptomatology of MS has previously been reported in large sample registry ...studies; however, some symptoms may be underreported in registries based on clinician-reported outcomes and how the symptoms are associated with quality of life (QoL) are often not addressed.
The aim of this study was to comprehensively evaluate the frequency of selected MS related symptoms and their associations with disability and QoL in a large self-report study.
Methods
We conducted a cross-sectional questionnaire survey among all patients at the Danish Multiple Sclerosis Center, Copenhagen University Hospital, Denmark. The questionnaire included information on clinical and sociodemographic characteristics, descriptors of QoL and disability, as well as prevalence and severity of the following MS symptoms: impaired ambulation, spasticity, chronic pain, fatigue, bowel and bladder dysfunction, and sleep disturbances.
Results
Questionnaires were returned by 2244/3606 (62%). Participants without MS diagnosis or incomplete questionnaires were excluded,
n
= 235. A total of 2009 questionnaires were included for analysis (mean age 49.4 years; mean disease duration 11.7 years; and 69% were women).
The most frequently reported symptoms were bowel and bladder dysfunction (74%), fatigue (66%), sleep disturbances (59%), spasticity (51%) and impaired ambulation (38%). With exception of fatigue and sleep disturbances, all other symptoms increased in severity with higher disability level. Invisible symptoms (also referred to as hidden symptoms) such as fatigue, pain and sleep disturbances had the strongest associations with the overall QoL.
Conclusion
We found invisible symptoms highly prevalent, even at mild disability levels. Fatigue, pain and sleep disturbances had the strongest associations with the overall QoL and were more frequently reported in our study compared with previous registry-based studies. These symptoms may be underreported in registries based on clinician reported outcomes, which emphasizes the importance of including standardized patient reported outcomes in nationwide registries to better understand the impact of the symptom burden in MS.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent studies have shown that sub-lethal doses of herbicides may affect plant flowering, however, no study has established a direct relationship between the concentrations of deposited herbicide and ...plant flowering. Here the aim was to investigate the relationship between herbicide spray drift deposited on non-target plants and plant flowering in a realistic agro-ecosystem setting. The concentrations of the herbicide glyphosate deposited on plants were estimated by measuring the concentration of a dye tracer applied together with the herbicide. The estimated maximal and average deposition of glyphosate within the experimental area corresponded to 30 g glyphosate/ha (2.08% of the label rate of 1440 g a.i./ha) and 2.4 g glyphosate/ha (0.15% label rate), respectively, and the concentrations decreased rapidly with increasing distance from the spraying track. However, there were not a unique relation between distance and deposition, which indicate that heterogeneities of turbulence, wind speed and/or direction can strongly influence the deposition from 1 min to another during spraying. The effects of glyphosate on cumulative flower numbers and flowering time were modelled using Gompertz growth models on four non-target species. Glyphosate had a significantly negative effect on the cumulative number of flowers on Trifolium pratense and Lotus corniculatus, whereas there were no significant effects on Trifolium repens, and a positive, but non-significant, effect on number of flowers on Cichorium intybus. Glyphosate did not affect the flowering time of any of the four species significantly. Lack of floral resources is known to be of major importance for pollinator declines. The implications of the presented results for pesticide risk assessment are discussed.
Display omitted
•The aim was to investigate the effect of herbicides in an agro-ecosystem setting.•The levels of glyphosate in the field were estimated by measuring a dye tracer.•The deposition of glyphosate decreased rapidly with increasing distance.•Glyphosate had a significantly negative effect on the cumulative number of flowers.•Glyphosate did not affect the flowering time on any of the species significantly.
In recent years, international working groups, mainly from the International Electrotechnical Commission (IEC) and the Western Electricity Coordinating Council (WECC), have made a major effort to ...develop generic —also known as simplified or standard— dynamic wind turbine models to be used for power system stability analysis. These models are required by power system operators to conduct the planning and operation activities of their networks since the use of detailed manufacturer models is not practical. This paper presents a comprehensive review of the work done in this field, based on the results obtained by IEC and WECC working groups in the course of their research, which have motivated the publication of the IEC 61400-27 in February 2015. The final published versions of the generic models developed according to the existing four wind turbine technology types are detailed, highlighting the subsequent changes made during the development phase. The main differences between IEC and WECC generic models are also analyzed. Not only is the final model structure presented but we also provide a complete description of the physical behavior of wind turbines facing power system stability problems. Results are thus of great interest to grid operators, software developers, wind farm owners and researchers focused on the integration of wind energy into power systems.
Milk fatty acid composition is gaining interest in the Danish dairy industry both to develop new dairy products and as a management tool. To be able to implement milk fatty acid (FA) composition in ...the breeding program, it is important to know the correlations with the traits in the breeding goal. To estimate these correlations, we measured milk fat composition in Danish Holstein (DH) and Danish Jersey (DJ) cattle breeds using mid-infrared spectroscopy. Breeding values were estimated for specific FA and for groups of FA. Correlations with the estimated breeding values (EBV) underlying the Nordic Total Merit index (NTM) were calculated within breed. For both DH and DJ, we showed that FA EBV had moderate correlations with the NTM and production traits. For both DH and DJ, the correlation of FA EBV and NTM were in the same direction, except for C16:0 (0 in DH, 0.23 in DJ). A few correlations differed between DH and DJ. The correlation between claw health index and C18:0 was negative in DH (−0.09) but positive in DJ (0.12). In addition, some correlations were not significant in DH but were significant in DJ. The correlations between udder health index and long-chain FA, trans FA, C16:0, and C18:0 were not significant in DH (−0.05 to 0.02), but were significant in DJ (−0.17, −0.15, 0.14, and −0.16, respectively). For both DH and DJ, the correlations between FA EBV and nonproduction traits were low. This implies that it is possible to breed for a different fat composition in the milk without affecting the nonproduction traits in the breeding goal.
Social delphinids employ a vocal repertoire of clicks for echolocation and whistles for communication. Conversely, the less social and acoustically cryptic harbour porpoises (Phocoena phocoena) only ...produce narrow-band high-frequency (NBHF) clicks with properties that appear poorly suited for communication. Nevertheless, these small odontocetes likely mediate social interactions, such as mate choice and mother-calf contact, with sound. Here, we deployed six tags (DTAG3) on wild porpoises in Danish waters for a total of 96 hours to investigate if the patterns and use of stereotyped NBHF click trains are consistent with a communication function. We show that wild porpoises produce frequent (up to 27 • min
), high-repetition rate click series with repetition rates and output levels different from those of foraging buzzes. These sounds are produced in bouts and frequently co-occur with emission of similar sounds by nearby conspecifics, audible on the tags for >10% of the time. These results suggest that social interactions are more important to this species than their limited social encounters at the surface may indicate and that these interactions are mediated by at least two broad categories of calls composed of short, high-repetition rate click trains that may encode information via the repetition rate of their stereotyped NBHF clicks.
This paper examines the role of grant size in research funding. There is an increasing focus in a number of countries on larger grant forms, such as centers of excellence, and in some cases also ...increases in the size of individual project grants. Among the rationales for this are economies of scale in research and redistribution of resources towards top researchers in order to increases scientific productivity and pathbreaking research. However, there may potentially also be negative impacts of increasing funding size, and there is limited empirical evidence on the actual consequences of increases in size. In this paper we critically examine the rationales behind increases in funding size and the empirical evidence on the impacts of size in research funding. Our goal here is to present a more coherent view of the potential impacts of these initiatives, both positive and negative, that can help inform funding design.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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