| 1. |
- Ferrando, Carlos, et al.
(författare)
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Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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| 2. |
- Colomé, Núria, et al.
(författare)
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Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis
- 2022
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Ingår i: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 251
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Tidskriftsartikel (refereegranskat)abstract
- Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.
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| 3. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 8. |
- Fuentes, Manuel, et al.
(författare)
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Exploring High-Throughput Immunoassays for Biomarker Validation in Rheumatic Diseases in the Context of the Human Proteome Project
- 2023
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 22:4, s. 1105-1115
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatic diseases are high prevalence pathologies with different etiology and evolution and low sensitivity in clinical diagnosis. Therefore, it is necessary to develop an early diagnosis method which allows personalized treatment, depending on the specific pathology. The biology/disease initiative, at Human Proteome Project, is an integrative approach to identify relevant proteins in the human proteome associated with pathologies. A previously reported literature data mining analysis, which identified proteins related to osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PSA) was used to establish a systematic prioritization of potential biomarkers candidates for further evaluation by functional proteomics studies. The aim was to study the protein profile of serum samples from patients with rheumatic diseases such as OA, RA, and PSA. To achieve this goal, customized antibody microarrays (containing 151 antibodies targeting 121 specific proteins) were used to identify biomarkers related to early and specific diagnosis in a screening of 960 serum samples (nondepleted) (OA, n = 480; RA, n = 192; PSA, n = 288). This functional proteomics screening has allowed the determination of a panel (30 serum proteins) as potential biomarkers for these rheumatic diseases, displaying receiver operating characteristics curves with area under the curve values of 80-90%.
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| 9. |
- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 10. |
- Juanes-Velasco, Pablo, et al.
(författare)
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Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary The early diagnosis of leptomeningeal disease is a challenge because it is asymptomatic in the early stages. Consequently, it is important to identify a panel of biomarkers to help in its diagnosis and/or prognosis. For this purpose, we explored a multipronged proteomics approach in cerebrospinal fluid (CSF) to determine a potential panel of biomarkers. Thus, a systematic and exhaustive characterization of more than 300 CSF samples was performed by an integrated approach by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and functional proteomics analysis to establish protein profiles, which were useful for developing a panel of biomarkers validated by in silico approaches. In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.
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| 11. |
- Menditto, Enrica, et al.
(författare)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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Ingår i: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 12. |
- Vialas, Vital, et al.
(författare)
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A multicentric study to evaluate the use of relative retention times in targeted proteomics
- 2017
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 152, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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| 13. |
- Andreassi, Maria Grazia, et al.
(författare)
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A Longitudinal Study of Individual Radiation Responses in Pediatric Patients Treated with Proton and Photon Radiotherapy, and Interventional Cardiology : Rationale and Research Protocol of the HARMONIC Project
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:9, s. 8416-
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Tidskriftsartikel (refereegranskat)abstract
- The Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy (photon and proton) in Pediatrics (HARMONIC) is a five-year project funded by the European Commission that aimed to improve the understanding of the long-term ionizing radiation (IR) risks for pediatric patients. In this paper, we provide a detailed overview of the rationale, design, and methods for the biological aspect of the project with objectives to provide a mechanistic understanding of the molecular pathways involved in the IR response and to identify potential predictive biomarkers of individual response involved in long-term health risks. Biological samples will be collected at three time points: before the first exposure, at the end of the exposure, and one year after the exposure. The average whole-body dose, the dose to the target organ, and the dose to some important out-of-field organs will be estimated. State-of-the-art analytical methods will be used to assess the levels of a set of known biomarkers and also explore high-resolution approaches of proteomics and miRNA transcriptomes to provide an integrated assessment. By using bioinformatics and systems biology, biological pathways and novel pathways involved in the response to IR exposure will be deciphered.
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| 14. |
- Blaess, Julien, et al.
(författare)
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Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE) : consensus by an international task force
- 2024
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Ingår i: RMD Open. - : BMJ Publishing Group Ltd. - 2056-5933. ; 10:2
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE.METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus.RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals.CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.
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| 15. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 16. |
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| 17. |
- Diez, Paula, et al.
(författare)
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Integration of Proteomics and Transcriptomics Data Sets for the Analysis of a Lymphoma B-Cell Line in the Context of the Chromosome-Centric Human Proteome Project
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3530-3540
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive study of the molecular active landscape of human cells can be undertaken to integrate two different but complementary perspectives: transcriptomics, and proteomics. After the genome era, proteomics has emerged as a powerful tool to simultaneously identify and characterize the compendium of thousands of different proteins active in a cell. Thus, the Chromosome-centric Human Proteome Project (C-HPP) is promoting a full characterization of the human proteome combining high-throughput proteomics with the data derived from genome-wide expression profiling of protein-coding genes. Here we present a full proteomic profiling of a human lymphoma B-cell line (Ramos) performed using a nanoUPLC-LTQ-Orbitrap Velos proteomic platform, combined to an in-depth transcriptomic profiling of the same cell type. Data are available via ProteomeXchange with identifier PXD001933. Integration of the proteomic and transcriptomic data sets revealed a 94% overlap in the proteins identified by both -omics approaches. Moreover, functional enrichment analysis of the proteomic profiles showed an enrichment of several functions directly related to the biological and morphological characteristics of B-cells. In turn, about 30% of all protein-coding genes present in the whole human genome were identified as being expressed by the Ramos cells (stable average of 30% genes along all the chromosomes), revealing the size of the protein expression-set present in one specific human cell type. Additionally, the identification of missing proteins in our data sets has been reported, highlighting the power of the approach. Also, a comparison between neXtProt and UniProt database searches has been performed. In summary, our transcriptomic and proteomic experimental profiling provided a high coverage report of the expressed proteome from a human lymphoma B-cell type with a clear insight into the biological processes that characterized these cells. In this way, we demonstrated the usefulness of combining -omics for a comprehensive characterization of specific biological systems.
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| 18. |
- Helbig, Manuel, et al.
(författare)
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Integrating continuous atmospheric boundary layer and tower-based flux measurements to advance understanding of land-atmosphere interactions
- 2021
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923. ; 307
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Forskningsöversikt (refereegranskat)abstract
- The atmospheric boundary layer mediates the exchange of energy, matter, and momentum between the land surface and the free troposphere, integrating a range of physical, chemical, and biological processes and is defined as the lowest layer of the atmosphere (ranging from a few meters to 3 km). In this review, we investigate how continuous, automated observations of the atmospheric boundary layer can enhance the scientific value of co-located eddy covariance measurements of land-atmosphere fluxes of carbon, water, and energy, as are being made at FLUXNET sites worldwide. We highlight four key opportunities to integrate tower-based flux measurements with continuous, long-term atmospheric boundary layer measurements: (1) to interpret surface flux and atmospheric boundary layer exchange dynamics and feedbacks at flux tower sites, (2) to support flux footprint modelling, the interpretation of surface fluxes in heterogeneous and mountainous terrain, and quality control of eddy covariance flux measurements, (3) to support regional-scale modeling and upscaling of surface fluxes to continental scales, and (4) to quantify land-atmosphere coupling and validate its representation in Earth system models. Adding a suite of atmospheric boundary layer measurements to eddy covariance flux tower sites, and supporting the sharing of these data to tower networks, would allow the Earth science community to address new emerging research questions, better interpret ongoing flux tower measurements, and would present novel opportunities for collaborations between FLUXNET scientists and atmospheric and remote sensing scientists.
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| 19. |
- Henjes, Frauke, et al.
(författare)
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Analysis of Autoantibody Profiles in Osteoarthritis Using Comprehensive Protein Array Concepts
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:11, s. 5218-5229
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) is the most common rheumatic disease and one of the most disabling pathologies worldwide. To date, the diagnostic methods of OA are very limited, and there are no available medications capable of halting its characteristic cartilage degeneration. Therefore, there is a significant interest in new biomarkers useful for the early diagnosis, prognosis, and therapeutic monitoring. In the recent years, protein microarrays have emerged as a powerful proteomic tool to search for new biomarkers. In this study, we have used two concepts for generating protein arrays, antigen microarrays, and NAPPA (nucleic acid programmable protein arrays), to characterize differential autoantibody profiles in a set of 62 samples from OA, rheumatoid arthritis (RA), and healthy controls. An untargeted screen was performed on 3840 protein fragments spotted on planar antigen arrays, and 373 antigens were selected for validation on bead-based arrays. In the NAPPA approach, a targeted screening was performed on 80 preselected proteins. The autoantibody targeting CHST14 was validated by ELISA in the same set of patients. Altogether, nine and seven disease related autoantibody target candidates were identified, and this work demonstrates a combination of these two array concepts for biomarker discovery and their usefulness for characterizing disease-specific autoantibody profiles.
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| 20. |
- Horvatovich, Péter, et al.
(författare)
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In vitro Transcription/Translation System: A Versatile Tool in the Search for Missing Proteins
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3441-3451
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 18% of all human genes purported to encode proteins have not been directly evidenced at the protein level, according to the validation criteria established by neXtProt, and are considered as “missing” proteins. One of the goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to identify as many of these “missing” proteins as possible in human samples using mass spectrometry-based methods. To further this goal, a consortium of C–HPP teams (chromosomes 5, 10, 16 and 19) has joined forces to devise new strategies to identify “missing” proteins by use of a cell-free in vitro transcription/translation system (IVTT). The proposed strategy employs LC-MS/MS data-dependent acquisition (DDA) and targeted selective reaction monitoring (SRM) methods to scrutinize low complexity samples derived from IVTT translation. The optimized assays are then applied to identify “missing” proteins in human cells and tissues. We describe the approach and show proof-of-concept results for development of LC-SRM assays for identification of eighteen “missing” proteins. We believe that the IVTT system, when coupled with downstream mass spectrometric identification, can be applied to identify proteins that have eluded more traditional methods of detection.
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| 21. |
- Horvatovich, Peter, et al.
(författare)
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Quest for Missing Proteins : Update 2015 on Chromosome-Centric Human Proteome Project
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3415-3431
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information.
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| 22. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 23. |
- Megido, Loerto, et al.
(författare)
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Understanding and utilizing the biomolecule/nanosystems interface: Soft materials and coatings for controlled drug release
- 2017
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Ingår i: Nanotechnologies in Preventive and Regenerative Medicine: An Emerging Big Picture. - 9780323480642 ; , s. 244-260
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Combining biomolecules with materials used in medicine allows for local control of the biological response and can be used for modulating the host immune response, a major challenge in the efficacy of many medical devices. In Subchapter 3.1, we will review different methods used to attach biomolecules to materials, focusing on protein conjugation methods. We will begin by describing noncovalent immobilization strategies, including encapsulation within biomaterials and adsorption to material surfaces. We will then discuss strategies to covalently attach biomolecules to materials via the use of specific functional groups, thus enhancing the stability of the interaction. Finally, we will describe emerging methods to site specifically immobilize biomolecules to materials such that proteins are presented in an oriented manner, improving their overall functionality. Throughout the subchapter, we will emphasize the advantages and disadvantages of each technique, successes achieved, as well as the challenges remaining in this growing field.During last years, increasing development of nanoparticles as targeted drug delivery agents, has led to a wide amount of studies involving their characterization to the application as novel therapeutic agents. Hence, the nanoparticles interact with biological environments when they enter in the human body, and then proteins bind to the nanomaterial surface forming the protein corona. Protein corona has a great relevance in the interaction and function of the nanoparticle-drug conjugates. In fact, its characterization is one of the main challenges for nanoscience development. Herein, it is reviewed the main proteomic methods described for quantify and qualify the protein corona formed around nanoparticles to better understand the process of interaction with the biological media, and to decipher key parameters to control the effects of the protein corona.In Subchapter 3.3, the structure and working principles of coatings for controlled drug release in oral drug administration are presented. The release mechanisms, including diffusion, dissolution, osmotic pumping, and swelling are described. The soft materials used in the majority of controlled drug release formulations are natural and synthetic polymers. They are presented here and examples of specific polymers applied in controlled release formulations are provided. There is also a section containing characterization of soft materials using in situ electron microscopy for studying water transport through coatings at high-spatial resolution. The reason for this is that the detailed properties and release mechanisms of the controlled release depend on the material nanostructure. The in situ characterization gives access not only the information about the nanostructure but also the direct correlation between structure and properties on different length scales. Finally, an overview of the present major challenges and future possibilities concerning controlled drug release formulations is presented.Targeting cancer cells with functional nanoprobes possessing a targeting drug unit and an imaging moiety carries great potential for early detection, accurate diagnosis, and targeted therapy of various diseases. Given their nanoscopic dimensions, ultrasmall particles ( < 100nm) are in general well suited for interactions with the cells; however, the current challenge of the nanomedicine is to transform inorganic nanoparticles of metals (e.g., gold) or metal oxide (e.g., magnetite) into signal-generating vectors. Engineered nanostructures can act as vehicles for a large number of signaling centers and/or targeting units thereby offering unique opportunity to enhance the sensitivity by locally enhancing the density of signal groups. For this purpose, creation of surface groups enabling chemical attachment of antibodies or other targeting biomolecules are essential that will allow the delivery of therapeutic payloads to the diseased sites. Multimodal nanoprobes functionalized with different diagnostic and therapeutic options within a single nanoparticle followed by their functionalization with organic ligands and biomolecules can provide specific uptake and high sensitivity toward anatomical information. However, the vision of making clinical theranostics a routine clinical procedure is encumbered by limited stability of complex nanoparticles in biological milieu and lack of standardization of therapy response. Despite the widely acclaimed advantages of integrating diagnostic imaging, drug delivery, and therapeutic monitoring in a single nanotheranostic probe, the clinical utilization of engineered nanoprobes demands concerted efforts in the domains of nanoparticle and surface chemistry/charge, new chelator ligands, pharmaceutical technology, radioactive labeling of nanovectors, biokinetics, and pharmacodynamics of nanoprobes, and biological tests (cell tests and animal models).
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| 24. |
- Rajatheva, Nandana, et al.
(författare)
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Scoring the Terabit/s Goal:Broadband Connectivity in 6G
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper explores the road to vastly improving the broadband connectivity in future 6G wireless systems. Different categories of use cases are considered, from extreme capacity with peak data rates up to 1 Tbps, to raising the typical data rates by orders-of-magnitude, and supporting broadband connectivity at railway speeds up to 1000 km/h. To achieve these, not only the terrestrial networks will be evolved but they will also be integrated with satellite networks, all facilitating autonomous systems and various interconnected structures. We believe that several categories of enablers at the infrastructure, spectrum, and protocol/algorithmic levels are required to realize the connectivity goals in 6G. At the infrastructure level, we consider ultra-massive MIMO technology (possibly implemented using holographic radio), intelligent reflecting surfaces, user-centric cell-free networking, integrated access and backhaul, and integrated space and terrestrial networks. At the spectrum level, the network must seamlessly utilize sub-6 GHz bands for coverage and spatial multiplexing of many devices, while higher bands will be used for pushing the peak rates of point-to-point links. The latter path will lead to (sub-)Terahertz communications complemented by visible light communications in specific scenarios. At the protocol/algorithmic level, the enablers include improved coding, modulation, and waveforms to achieve lower latency, higher reliability, and reduced complexity. The resource efficiency can be further improved by using various combinations of full-duplex radios, interference management based on rate-splitting, machine-learning based optimization, coded caching, and broadcasting. Finally, the three levels of enablers must be utilized also to provide full-coverage broadband connectivity which must be one of the key outcomes of 6G.
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| 25. |
- Rajatheva, Nandana, et al.
(författare)
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White Paper on Broadband Connectivity in 6G
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This white paper explores the road to implementing broadband connectivity in future 6G wireless systems. Different categories of use cases are considered, from extreme capacity with peak data rates up to 1 Tbps, to raising the typical data rates by orders-of-magnitude, to support broadband connectivity at railway speeds up to 1000 km/h. To achieve these goals, not only the terrestrial networks will be evolved but they will also be integrated with satellite networks, all facilitating autonomous systems and various interconnected structures.We believe that several categories of enablers at the infrastructure, spectrum, and protocol/ algorithmic levels are required to realize the intended broadband connectivity goals in 6G. At the infrastructure level, we consider ultra-massive MIMO technology (possibly implemented using holographic radio), intelligent reflecting surfaces, user-centric and scalable cell-free networking, integrated access and backhaul, and integrated space and terrestrial networks. At the spectrum level, the network must seamlessly utilize sub-6 GHz bands for coverage and spatial multiplexing of many devices, while higher bands will be used for pushing the peak rates of point-to-point links. The latter path will lead to THz communications complemented by visible light communications in specific scenarios. At the protocol/algorithmic level, the enablers include improved coding, modulation, and waveforms to achieve lower latencies, higher reliability, and reduced complexity. Different options will be needed to optimally support different use cases. The resource efficiency can be further improved by using various combinations of full-duplex radios, interference management based on rate-splitting, machine-learning-based optimization, coded caching, and broadcasting.
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