| 1. |
- Chaudhari, Aditi, et al.
(författare)
-
Hepatic deletion of p110α and p85α results in insulin resistance despite sustained IRS1-associated phosphatidylinositol kinase activity
- 2017
-
Ingår i: F1000 Research. - : Faculty of 1000 Ltd.. - 2046-1402 .- 1759-796X. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Class IA phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is an integral mediator of insulin signaling. The p110 catalytic and p85 regulatory subunits of PI3K are the products of separate genes, and while they come together to make the active heterodimer, they have opposing roles in insulin signaling and action. Deletion of hepatic p110α results in an impaired insulin signal and severe insulin resistance, whereas deletion of hepatic p85α results in improved insulin sensitivity due to sustained levels of phosphatidylinositol (3,4,5)-trisphosphate. Here, we created mice with combined hepatic deletion of p110α and p85α (L-DKO) to study the impact on insulin signaling and whole body glucose homeostasis.Methods: Six-week old male flox control and L-DKO mice were studied over a period of 18 weeks, during which weight and glucose levels were monitored, and glucose tolerance tests, insulin tolerance test and pyruvate tolerance test were performed. Fasting insulin, insulin signaling mediators, PI3K activity and insulin receptor substrate (IRS)1-associated phosphatidylinositol kinase activity were examined at 10 weeks. Liver, muscle and white adipose tissue weight was recorded at 10 weeks and 25 weeks.Results: The L-DKO mice showed a blunted insulin signal downstream of PI3K, developed markedly impaired glucose tolerance, hyperinsulinemia and had decreased liver and adipose tissue weights. Surprisingly, however, these mice displayed normal hepatic glucose production, normal insulin tolerance, and intact IRS1-associated phosphatidylinositol kinase activity without compensatory upregulated signaling of other classes of PI3K.Conclusions: The data demonstrate an unexpectedly overall mild metabolic phenotype of the L-DKO mice, suggesting that lipid kinases other than PI3Ks might partially compensate for the loss of p110α/p85α by signaling through other nodes than Akt/Protein Kinase B.
|
|
| 2. |
- Corciulo, Carmen, et al.
(författare)
-
Pulsed administration for physiological estrogen replacement in mice
- 2021
-
Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402 .- 1759-796X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid.
|
|
| 3. |
- Martins Dos Santos, Vitor, et al.
(författare)
-
Systems Biology in ELIXIR: modelling in the spotlight
- 2022
-
Ingår i: F1000Research. - : F1000 Research Ltd. - 1759-796X .- 2046-1402. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR's future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives.
|
|
| 4. |
- Mülleder, Michael, et al.
(författare)
-
Saccharomyces cerevisiae single-copy plasmids for auxotrophy compensation, multiple marker selection, and for designing metabolically cooperating communities
- 2016
-
Ingår i: F1000Research. - : F1000 Research Ltd. - 1759-796X .- 2046-1402. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Auxotrophic markers are useful tools in cloning and genome editing, enable a large spectrum of genetic techniques, as well as facilitate the study of metabolite exchange interactions in microbial communities. If unused background auxotrophies are left uncomplemented however, yeast cells need to be grown in nutrient supplemented or rich growth media compositions, which precludes the analysis of biosynthetic metabolism, and which leads to a profound impact on physiology and gene expression. Here we present a series of 23 centromeric plasmids designed to restore prototrophy in typical Saccharomyces cerevisiae laboratory strains. The 23 single-copy plasmids complement for deficiencies in HIS3, LEU2, URA3, MET17 or LYS2 genes and in their combinations, to match the auxotrophic background of the popular functional-genomic yeast libraries that are based on the S288c strain. The plasmids are further suitable for designing self-establishing metabolically cooperating (SeMeCo) communities, and possess a uniform multiple cloning site to exploit multiple parallel selection markers in protein expression experiments.
|
|
| 5. |
- Abdekhodaie, Ehsan, et al.
(författare)
-
WordCommentsAnalyzer : A windows software tool for qualitative research
- 2018
-
Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- There is a lack of free software that provides a professional and smooth experience in text editing and markup for qualitative data analysis. Word processing software like Microsoft Word provides a good editing experience, allowing the researcher to effortlessly add comments to text portions. However, organizing the keywords and categories in the comments can become a more difficult task when the amount of data increases. We present WordCommentsAnalyzer, a software tool that is written in C# using .NET Framework and OpenXml, which helps a qualitative researcher to organize codes when using Microsoft Word as the primary text markup software. WordCommentsAnalyzer provides an effective user interface to count codes, to organize codes in a code hierarchy, and to see various data extracts belonging to each code. It also offers basic visualization tools. We illustrate how to use this software by conducting a preliminary content analysis on Tweets with the #successfulaging hashtag. We also demonstrate that the software has satisfactory performance on a large dataset of Iranian journals abstracts. We hope this open-source software will facilitate qualitative data analysis by researchers who are interested in using Word for this purpose.
|
|
| 6. |
- Af Petersens, M, et al.
(författare)
-
Workplace exposure to carbon dioxide during routine laparoscopy - is it safe?
- 2020
-
Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402. ; 9, s. 571-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive surgeries have increased dramatically during the last decades. Carbon dioxide (CO2) is the gas used for insufflation during laparoscopies, creating space and visibility. The CO2 leaks into ambient air through ports where instruments are inserted. If the CO2 reaches a certain concentration it affects personnel health. There are national occupational exposure limits (OEL) for CO2, including a level limit value (LLV) of 5000 ppm. We are not aware of any previous studies addressing occupational exposure to CO2 during laparoscopies. The aim of this study was to assess the compliance to national OELs for CO2 during laparoscopies. Methods: A gas detector was placed in the breathing zone of personnel in the operating theatre. The detector measured CO2 concentrations every tenth minute during laparoscopies in three locations. Results: During 27 laparoscopies, the measured CO2 reached a maximum concentration of 1100 ppm, less than one fourth of the LLV. Median CO2 concentration was 700 ppm. Conclusion: Results show that the occupational exposure to CO2 during laparoscopies is well below set OELs. Our findings support personnel safety associated with routine use of CO2 during laparoscopies.
|
|
| 7. |
- Andeer, Robin, et al.
(författare)
-
Chanjo : Clincal grade sequence coverage analysis
- 2020
-
Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Coverage analysis is essential when analysing massive parallel sequencing (MPS) data. The analysis indicates existence of false negatives or positives in a region of interest or poorly covered genomic regions. There are several tools that have excellent performance when doing coverage analysis on a few samples with predefined regions. However, there is no current tool for collecting samples over a longer period of time for aggregated coverage analysis of multiple samples or sequencing methods. Furthermore, current coverage analysis tools do not generate customized coverage reports or enable exploratory coverage analysis without extensive bioinformatic skill and access to the original alignment files. We present Chanjo, a user friendly coverage analysis tool for persistent storage of coverage data, that, accompanied with Chanjo Report, produces coverage reports that summarize coverage data for predefined regions in an elegant manner. Chanjo Report can produce both structured coverage reports and dynamic reports tailored to a subset of genomic regions, coverage cut-offs or samples. Chanjo stores data in an SQL database where thousands of samples can be added over time, which allows for aggregate queries to discover problematic regions. Chanjo is well tested, supports whole exome and genome sequencing, and follows common UNIX standards, allowing for easy integration into existing pipelines. Chanjo is easy to install and operate, and provides a solution for persistent coverage analysis and clinical-grade reporting. It makes it easy to set up a local database and automate the addition of multiple samples and report generation. To our knowledge there is no other tool with matching capabilities. Chanjo handles the common file formats in genetics, such as BED and BAM, and makes it easy to produce PDF coverage reports that are highly valuable for individuals with limited bioinformatic expertise. We believe Chanjo to be a vital tool for clinicians and researchers performing MPS analysis.
|
|
| 8. |
- Angers-Loustau, A., et al.
(författare)
-
The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies
- 2018
-
Ingår i: F1000Research. - : F1000 Research Ltd. - 2046-1402. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms. In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed. NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced. Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process. This concept was explored as part of a workshop on "Next-generation sequencing technologies and antimicrobial resistance" held October 4-5 2017. Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a "One Health" approach.
|
|
| 9. |
- Anzt, Hartwig, et al.
(författare)
-
An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action
- 2020
-
Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.
|
|
| 10. |
- Auffray, C., et al.
(författare)
-
COVID-19 and beyond : a call for action and audacious solidarity to all the citizens and nations, it is humanity’s fight
- 2020
-
Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9, s. 1130-18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 was facilitated by the increasing intensity of air travel, urban congestion and human contact during the past decades. Until therapies and vaccines are available, tests for virus exposure, confinement and distancing measures have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. Self-organizing initiatives by scientists and citizens are developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies.
|
|
