| 1. |
- Tabiri, S, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
- Bravo, L, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Sliz, E., et al.
(author)
-
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Akkoyun, S., et al.
(author)
-
AGATA - Advanced GAmma Tracking Array
- 2012
-
In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087 .- 1872-9576. ; 668, s. 26-58
-
Journal article (peer-reviewed)abstract
- The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation γ-ray spectrometer. AGATA is based on the technique of γ-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a γ ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of γ-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector- response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer. © 2011 Elsevier B.V. All rights reserved.
|
|
| 11. |
- Gaur, V K, et al.
(author)
-
Sustainable strategies for combating hydrocarbon pollution : Special emphasis on mobil oil bioremediation
- 2022
-
In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 832
-
Journal article (peer-reviewed)abstract
- The global rise in industrialization and vehicularization has led to the increasing trend in the use of different crude oil types. Among these mobil oil has major application in automobiles and different machines. The combustion of mobil oil renders a non-usable form that ultimately enters the environment thereby causing problems to environmental health. The aliphatic and aromatic hydrocarbon fraction of mobil oil has serious human and environmental health hazards. These components upon interaction with soil affect its fertility and microbial diversity. The recent advancement in the omics approach viz. metagenomics, metatranscriptomics and metaproteomics has led to increased efficiency for the use of microbial based remediation strategy. Additionally, the use of biosurfactants further aids in increasing the bioavailability and thus biodegradation of crude oil constituents. The combination of more than one approach could serve as an effective tool for efficient reduction of oil contamination from diverse ecosystems. To the best of our knowledge only a few publications on mobil oil have been published in the last decade. This systematic review could be extremely useful in designing a micro-bioremediation strategy for aquatic and terrestrial ecosystems contaminated with mobil oil or petroleum hydrocarbons that is both efficient and feasible. The state-of-art information and future research
|
|
| 12. |
|
|
| 13. |
- Devda, V., et al.
(author)
-
Recovery of resources from industrial wastewater employing electrochemical technologies : status, advancements and perspectives
- 2021
-
In: Bioengineered. - : Taylor & Francis Group. - 2165-5979 .- 2165-5987. ; 12:1, s. 4697-4718
-
Journal article (peer-reviewed)abstract
- In the last two decades, water use has increased at twice the rate of population growth. The freshwater resources are getting polluted by contaminants like heavy metals, pesticides, hydrocarbons, organic waste, pathogens, fertilizers, and emerging pollutants. Globally more than 80% of the wastewater is released into the environment without proper treatment. Rapid industrialization has a dramatic effect on developing countries leading to significant losses to economic and health well-being in terms of toxicological impacts on humans and the environment through air, water, and soil pollution. This article provides an overview of physical, chemical, and biological processes to remove wastewater contaminants. A physical and/or chemical technique alone appears ineffective for recovering useful resources from wastewater containing complex components. There is a requirement for more processes or processes combined with membrane and biological processes to enhance operational efficiency and quality. More processes or those that are combined with biological and membrane-based processes are required to enhance operational efficiencies and quality. This paper intends to provide an exhaustive review of electrochemical technologies including microbial electrochemical technologies. It provides comprehensive information for the recovery of metals, nutrients, sulfur, hydrogen, and heat from industrial effluents. This article aims to give detailed information into the advancements in electrochemical processes to energy use, improve restoration performance, and achieve commercialization. It also covers bottlenecks and perspectives of this research area.
|
|
| 14. |
- Ngo, Ngo Valery, et al.
(author)
-
Reproductive health policy Saga: Restrictive abortion laws in low- and middle-income countries (LMICs), unnecessary cause of maternal mortality
- 2024
-
In: Health Care for Women International. - : Informa UK Limited. - 0739-9332 .- 1096-4665. ; 45:1, s. 5-23
-
Journal article (peer-reviewed)abstract
- Abortion is a common but controversial phenomenon globally. The discourse on the legality of abortion remains intricate, leaving a substantial number of women restricted from accessing safe abortion. There are evidence of an association between restrictive abortion laws, unsafe abortions, and maternal mortality in low-and middle-income countries (LMICs). We explore how restrictive abortion laws violate women's right to health and bodily integrity. We used Carol Bacchi's policy framework to analyze how restrictive abortion laws have been discursively framed (problematization); the assumptions that underpinned the representation; the consequences of the representation; what was left unproblematic; how the representation could be questioned, disrupted and replaced. We found that most of these laws are based on morality and the limited number of women in politics has made them objects rather than subjects in decision-making process. Therefore, we recommend a holistic approach to abortion laws with women leading the process to achieve reproductive justice.
|
|
| 15. |
- Ngwa, Henry Che, et al.
(author)
-
Burden of vaccine-preventable diseases, trends in vaccine coverage and current challenges in the implementation of the expanded program on immunization: A situation analysis of Cameroon
- 2022
-
In: Human Vaccines & Immunotherapeutics. - : Informa UK Limited. - 2164-5515 .- 2164-554X. ; 18:1
-
Journal article (peer-reviewed)abstract
- The discovery and development of vaccines remain one of the major successes of global health with millions of lives saved every year through routine vaccination. Although vaccines provide a safe and cost-effective solution to vaccine-preventable diseases (VPDs), VPDs are still a serious public health problem in most parts of the world, especially in sub-Saharan Africa (SSA) and Asia. In this review, we discuss the burden of VPDs and vaccine coverage several decades after the introduction of the Expanded Program on Immunization (EPI) in Cameroon. We also discuss how different factors affect the implementation of the EPI, highlighting context-specific factors such as the ongoing civil conflict in Cameroon, and the presence of other infectious diseases like COVID-19.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Alexander, Stephen P. H., et al.
(author)
-
The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
-
In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
-
Journal article (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
|
|
| 19. |
- Chan, Kai M. A., et al.
(author)
-
Levers and leverage points for pathways to sustainability
- 2020
-
In: People and Nature. - : Wiley. - 2575-8314. ; 2:3, s. 693-717
-
Journal article (peer-reviewed)abstract
- 1. Humanity is on a deeply unsustainable trajectory. We are exceeding planetary boundaries and unlikely to meet many international sustainable development goals and global environmental targets. Until recently, there was no broadly accepted framework of interventions that could ignite the transformations needed to achieve these desired targets and goals.2. As a component of the IPBES Global Assessment, we conducted an iterative expert deliberation process with an extensive review of scenarios and pathways to sustainability, including the broader literature on indirect drivers, social change and sustainability transformation. We asked, what are the most important elements of pathways to sustainability?3. Applying a social-ecological systems lens, we identified eight priority points for intervention (leverage points) and five overarching strategic actions and priority interventions (levers), which appear to be key to societal transformation. The eight leverage points are: (1) Visions of a good life, (2) Total consumption and waste, (3) Latent values of responsibility, (4) Inequalities, (5) Justice and inclusion in conservation, (6) Externalities from trade and other telecouplings, (7) Responsible technology, innovation and investment, and (8) Education and knowledge generation and sharing. The five intertwined levers can be applied across the eight leverage points and more broadly. These include: (A) Incentives and capacity building, (B) Coordination across sectors and jurisdictions, (C) Pre-emptive action, (D) Adaptive decision-making and (E) Environmental law and implementation. The levers and leverage points are all non-substitutable, and each enables others, likely leading to synergistic benefits.4. Transformative change towards sustainable pathways requires more than a simple scaling-up of sustainability initiatives-it entails addressing these levers and leverage points to change the fabric of legal, political, economic and other social systems. These levers and leverage points build upon those approved within the Global Assessment's Summary for Policymakers, with the aim of enabling leaders in government, business, civil society and academia to spark transformative changes towards a more just and sustainable world.
|
|
| 20. |
- Christopoulos, Arthur, et al.
(author)
-
THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
-
In: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
-
Research review (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
|
|
| 21. |
- Heinzel, T., et al.
(author)
-
A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression
- 1997
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 387:6628, s. 43-48
-
Journal article (peer-reviewed)abstract
- Transcriptional repression by nuclear receptors has been correlated to binding of the putative co-repressor, N-CoR. A complex has been identified that contains N-CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3, and which is required for both nuclear receptor- and Mad-dependent repression, but not for repression by transcription factors of the ets-domain family. These data predict that the ligand-induced switch of heterodimeric nuclear receptors from repressor to activator functions involves the exchange of complexes containing histone deacetylases with those that have histone acetylase activity.
|
|
| 22. |
- Hop, Paul J., et al.
(author)
-
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
-
In: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
|
|
| 23. |
|
|
| 24. |
- Kreibich, Heidi, et al.
(author)
-
Panta Rhei benchmark dataset : Socio-hydrological data of paired events of floods and droughts
- 2023
-
In: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 15:5, s. 2009-2023
-
Journal article (peer-reviewed)abstract
- As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions, and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e. two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed and in the quantity of socio-hydrological data. The benchmark dataset comprises (1) detailed review-style reports about the events and key processes between the two events of a pair; (2) the key data table containing variables that assess the indicators which characterize management shortcomings, hazard, exposure, vulnerability, and impacts of all events; and (3) a table of the indicators of change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators of change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses, e.g. focused on causal links between risk management; changes in hazard, exposure and vulnerability; and flood or drought impacts. The data can also be used for the development, calibration, and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al., 2023, 10.5880/GFZ.4.4.2023.001).
|
|
| 25. |
- Kreibich, Heidi, et al.
(author)
-
The challenge of unprecedented floods and droughts in risk management
- 2022
-
In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 608:7921, s. 80-86
-
Journal article (peer-reviewed)abstract
- Risk management has reduced vulnerability to floods and droughts globally, yet their impacts are still increasing. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Majek, O., et al.
(author)
-
How to follow the new EU Council recommendation and improve prostate cancer early detection: the Prostaforum 2022 declaration
- 2023
-
In: European Urology Open Science. - 2666-1691. ; 53, s. 106-108
-
Journal article (peer-reviewed)abstract
- An updated Council of the EU recommendation on cancer screening was adopted in December 2022 during the Czech EU presidency. The recommendation included prostate cancer as a suitable target disease for organised screening, and invited countries to proceed with piloting and further research. To support further discussions and actions to promote early detection of prostate cancer, an international conference in November 2022 (Prostaforum 2022) resulted in a joint declaration. Here we describe the EU policy background, summarise the preparation of the declaration and the key underlying evidence and expert recommendations, and report the text of the declaration. The declaration summarises the striking inequalities in prostate cancer burden in Europe and calls on all stakeholders to consider and support concrete steps for advancement of organised early detection of prostate cancer. Our aim is to request endorsement of the text and potential initiation of practical actions by all stakeholders to support the aims of the declaration.Patient summary: Prostate cancer is among the most frequent cancers and is one of the most common causes of cancer death among men. The European Union has recommended new pilot programmes for prostate cancer screening. The Prostaforum 2022 declaration invites all stakeholders to support this new recommendation with specific steps.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
|
|
| 29. |
- Martinez-Sanchez, LD, et al.
(author)
-
Epithelial RAC1-dependent cytoskeleton dynamics controls cell mechanics, cell shedding and barrier integrity in intestinal inflammation
- 2023
-
In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 72:2, s. 275-294
-
Journal article (peer-reviewed)abstract
- Increased apoptotic shedding has been linked to intestinal barrier dysfunction and development of inflammatory bowel diseases (IBD). In contrast, physiological cell shedding allows the renewal of the epithelial monolayer without compromising the barrier function. Here, we investigated the role of live cell extrusion in epithelial barrier alterations in IBD.DesignTaking advantage of conditional GGTase and RAC1 knockout mice in intestinal epithelial cells (Pggt1biΔIECandRac1iΔIECmice), intravital microscopy, immunostaining, mechanobiology, organoid techniques and RNA sequencing, we analysed cell shedding alterations within the intestinal epithelium. Moreover, we examined human gut tissue and intestinal organoids from patients with IBD for cell shedding alterations and RAC1 function.ResultsEpithelialPggt1bdeletion led to cytoskeleton rearrangement and tight junction redistribution, causing cell overcrowding due to arresting of cell shedding that finally resulted in epithelial leakage and spontaneous mucosal inflammation in the small and to a lesser extent in the large intestine. Both in vivo and in vitro studies (knockout mice, organoids) identified RAC1 as a GGTase target critically involved in prenylation-dependent cytoskeleton dynamics, cell mechanics and epithelial cell shedding. Moreover, inflamed areas of gut tissue from patients with IBD exhibited funnel-like structures, signs of arrested cell shedding and impaired RAC1 function. RAC1 inhibition in human intestinal organoids caused actin alterations compatible with arresting of cell shedding.ConclusionImpaired epithelial RAC1 function causes cell overcrowding and epithelial leakage thus inducing chronic intestinal inflammation. Epithelial RAC1 emerges as key regulator of cytoskeletal dynamics, cell mechanics and intestinal cell shedding. Modulation of RAC1 might be exploited for restoration of epithelial integrity in the gut of patients with IBD.
|
|
| 30. |
- Mishra, B., et al.
(author)
-
Engineering biocatalytic material for the remediation of pollutants : A comprehensive review
- 2020
-
In: Environmental Technology & Innovation. - : Elsevier B.V.. - 2352-1864. ; 20
-
Journal article (peer-reviewed)abstract
- Bioremediation through biotechnological interventions has attracted more attention among researchers in field of environmental pollution control and abatement. Various cutting-edge studies in area of protein engineering and synthetic biology offer a new platform for creation of innovative, advanced biological materials for its beneficial role in environmental pollution mitigation. Biocatalysis especially receives considerable attention as sustainable approach to resource recovery from waste along with elimination of pollutants. This paper focuses on updated developments in engineering of biocatalytic substances which can degrade pollutants of emerging concern. It also explains various classes of biocatalysts, their mechanisms of immobilization, and applications in terms of environmental pollutant remediation. Opportunities and challenges for future research have also been discussed.
|
|
| 31. |
- Ngo, D., et al.
(author)
-
Proteomic profiling reveals biomarkers and pathways in type 2 diabetes risk
- 2021
-
In: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:5
-
Journal article (peer-reviewed)abstract
- Recent advances in proteomic technologies have made high-throughput profiling of low-abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across 2 large longitudinal cohorts (n = 2839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic, and clinical data from humans to nominate 1 specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Furthermore, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing protein 2 (WFIKKN2) was, in turn, associated with fasting glucose, hemoglobin A1c, and HOMA-IR measurements in humans. In addition to identifying potentially novel disease markers and pathways in T2DM, we provide publicly available data to be leveraged for insights about gene function and disease pathogenesis in the context of human metabolism.
|
|
| 32. |
- Ngo, Debby, et al.
(author)
-
Proteomic profiling reveals novel biomarkers and pathways in yype 2 diabetes risk
- 2021
-
In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:5
-
Journal article (peer-reviewed)abstract
- Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .
|
|
| 33. |
|
|
| 34. |
- Pagan, C, et al.
(author)
-
The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.
- 2014
-
In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
-
Journal article (peer-reviewed)abstract
- Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.
|
|
| 35. |
- Papazafeiropoulos, Anastasios K., et al.
(author)
-
Performance of Massive MIMO Uplink With Zero-Forcing Receivers Under Delayed Channels
- 2017
-
In: IEEE Transactions on Vehicular Technology. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9545 .- 1939-9359. ; 66:4, s. 3158-3169
-
Journal article (peer-reviewed)abstract
- In this paper, we analyze the performance of the up-link communication of massive multicell multiple-input multiple-output (MIMO) systems under the effects of pilot contamination and delayed channels because of terminal mobility. The base stations (BSs) estimate the channels through the uplink training and then use zero-forcing (ZF) processing to decode the transmit signals from the users. The probability density function (pdf) of the signal-to-interference-plus-noise ratio (SINR) is derived for any finite number of antennas. From this pdf, we derive an achievable ergodic rate with a finite number of BS antennas in closed form. Insights into the impact of the Doppler shift (due to terminal mobility) at the low signal-to-noise ratio (SNR) regimes are exposed. In addition, the effects on the outage probability are investigated. Furthermore, the power scaling law and the asymptotic performance result by infinitely increasing the numbers of antennas and terminals (while their ratio is fixed) are provided. The numerical results demonstrate the performance loss for various Doppler shifts. Among the interesting observations revealed is that massive MIMO is favorable even under channel aging conditions.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- van Rheenen, W, et al.
(author)
-
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
-
Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
|
|
| 39. |
|
|
| 40. |
- Vornhagen, J., et al.
(author)
-
Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection
- 2018
-
In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 128:5, s. 1985-1999
-
Journal article (peer-reviewed)abstract
- Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and beta-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes.
|
|
| 41. |
- Zhang, Chengji, et al.
(author)
-
Lithium superoxide-based high rate Li-Air batteries enabled by Di-iridium sulfur bridge active sites
- 2023
-
In: Energy Storage Materials. - 2405-8289 .- 2405-8297. ; 60
-
Journal article (peer-reviewed)abstract
- Li-oxygen (Li-O2) batteries can potentially provide much higher energy density than Li-ion batteries; however, the practical application of these batteries is hindered due to several drawbacks such as low current rates and high overpotential for the charging process. In this paper, we report a novel Li-Air battery system that operates under high current rates (up to 1mAcm 2) with LiO2 as the primary discharge product instead of the commonly reported Li2O2. This LiO2 based battery at high rates is through a combination of an as-synthesized new onedimensional (1D) transition metal trichalcogenide mid-entropy alloy of SnIrS3.6 as a cathode catalyst and an electrolyte blend with a SnI2 bi-functional additive. It is revealed that SnIrS3.6 has a microporous structure composed of six- and five-coordinated metal atoms, forming octahedral and triangular bipyramids which has not been observed in other layered chalcogeide materials. DFT calculations reveal that the SnIrS3.6 structure can result in LiO2 formation through di-iridium sulfur bridge active sites that results in strong binding of O2 and LiO2 preventing disproportionation to Li2O2 and enabling high rates. This finding will open a new perspective in designing advanced LiO2-based Li-O2 batteries for real practices.
|
|
| 42. |
- Zou, L., et al.
(author)
-
Drug Metabolites Potently Inhibit Renal Organic Anion Transporters, OAT1 and OAT3
- 2021
-
In: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549. ; 110:1, s. 347-353
-
Journal article (peer-reviewed)abstract
- Human OAT1 and OAT3 play major roles in renal drug elimination and drug-drug interactions. However, there is little information on the interactions of drug metabolites with transporters. The goal of this study was to characterize the interactions of drug metabolites with OAT1 and OAT3 and compare their potencies of inhibition with those of their corresponding parent drugs. Using HEK293 cells stably transfected with OAT1 and OAT3, 25 drug metabolites and their corresponding parent drugs were screened for inhibitory effects on OAT1-and OAT3-mediated 6-carboxyfluorescein uptake at a screening concentration of 200 mu M for all but 3 compounds. 20 and 24 drug metabolites were identified as inhibitors (inhibition > 50%) of OAT1 and OAT3, respectively. Seven drug metabolites were potent inhibitors of either or both OAT1 and OAT3 with K-i values less than 1 mu M. 22 metabolites were more potent inhibitors of OAT3 than OAT1. Importantly, one drug and four metabolites were predicted to inhibit OAT3 at unbound plasma concentrations achieved clinically (C-max,C-u/K-i values >= 0.1). In conclusion, our study highlights the potential interactions of drug metabolites with OAT1 and OAT3 at clinically relevant concentrations, suggesting that drug metabolites may modulate therapeutic and adverse drug response by inhibiting renal drug transporters. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
|
|
