| 1. |
- Hatos, Andras, et al.
(författare)
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DisProt : intrinsic protein disorder annotation in 2020
- 2020
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
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Tidskriftsartikel (refereegranskat)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
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| 2. |
- Toth, Arnold, et al.
(författare)
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Microbleeds may expand acutely after traumatic brain injury
- 2016
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Ingår i: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 617, s. 207-212
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Susceptibility weighted imaging (SWI) is a very sensitive tool for the detection of microbleeds in traumatic brain injury (TBI). The number and extent of such traumatic microbleeds (TMBs) have been shown to correlate with the severity of the injury and the clinical outcome. However, the acute dynamics of TMBs have not been revealed so far. Since TBI is known to constitute dynamic pathological processes, we hypothesized that TMBs are not constant in their appearance, but may progress acutely after injury.Materials and methods: We present here five closed moderate/severe (Glasgow coma scale≤13) TBI patients who underwent SWI very early (average=23.4 h), and once again a week (average=185.8 h) after the injury. The TMBs were mapped at both time points by a conventional radiological approach and their numbers and volumes were measured with manual tracing tools by two observers. TMB counts and extents were compared between time points.Results: TMBs were detected in four patients, three of them displaying an apparent TMB change. In these patients, TMB confluence and apparent growth were detected in the corpus callosum, coronal radiation or subcortical white matter, while unchanged TMBs were also present. These changes caused a decrease in the TMB count associated with an increase in the overall TMB volume over time.Conclusion: We have found a compelling evidence that diffuse axonal injury-related microbleed development is not limited strictly to the moment of injury: the TMBs might expand in the acute phase of TBI. The timing of SWI acquisition may be relevant for optimizing the prognostic utility of this imaging biomarker.
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| 3. |
- Brasko, Csilla, et al.
(författare)
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Intelligent image-based in situ single-cell isolation
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
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| 4. |
- Büki, Andras, 1966-, et al.
(författare)
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Peptidergic innervation of human cerebral blood vessels and saccular aneurysms
- 1999
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Ingår i: Acta Neuropathologica. - : Springer. - 0001-6322 .- 1432-0533. ; 98:4, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- Peptidergic innervation of the human cerebral vasculature has not yet been described in detail and its role in the maintenance of cerebral autoregulation still needs to be established. Similarly, few data exist on the innervation of vascular malformations. The aim of this study was to clarify the peptidergic innervation patterns of human cerebral arteries of various sizes, and, for the first time, that of saccular aneurysms. Light microscopic study of whole-mount preparations of human cerebral arteries and aneurysm sacs resected either during tumor removal or after neck-clipping were carried out by means of silver-intensified light microscopic immunocytochemistry visualizing neuropeptide-Y, calcitonin gene-related peptide and substance P immunoreactivity. Systematic morphological investigations confirmed the presence of longitudinal fiber bundles on the adventitia and a network-like deeper peptidergic system at the adventitia-media border, while in smaller pial and intraparenchymal vessels, only sparse longitudinal immunopositive axons could be detected. The innervation pattern was totally absent in the wall of saccular aneurysms with the complete disappearance of peptidergic nerve fibers in some areas. To the best of our knowledge neither the disappearance of this network on small pial and intraparenchymal vessels, nor the absence of an innervation pattern in saccular aneurysms have been described before. Nonhomogeneous peptidergic innervation of the human cerebral vascular tree might be one of the factors responsible for the distinct autoregulatory properties of the capacitance and resistance vessels. Malfunction of this vasoregulatory system might lead to the impairment of autoregulation during pathological conditions such as subarachnoid hemorrhage.
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| 5. |
- Deierborg Olsson, Tomas, et al.
(författare)
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Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse.
- 2008
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 28, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Uncoupling protein 2 (UCP2) is upregulated in the brain after sublethal ischemia, and overexpression of UCP2 is neuroprotective in several models of neurodegenerative disease. We investigated if increased levels of UCP2 diminished neuronal damage after global brain ischemia by subjecting mice overexpressing UCP2 (UCP2/3tg) and wild-type littermates (wt) to a 12-min global ischemia. The histopathological outcome in the cortex, hippocampus, striatum, and thalamus was evaluated at 4 days of recovery, allowing maturation of the selective neuronal death. Global ischemia led to extensive cell death in the striatum, thalamus, and in the CA1 and CA2, and less-pronounced cell death in the CA3 and dentate gyrus (DG) hippocampal subfields. Histologic damage was significantly lower in the ventral posterolateral VPL and medial VPM thalamic nuclei in UCP2/3tg animals compared with wt. These thalamic regions showed a larger increase in UCP2 expression in UCP2/3tg compared with wt animals relative to the nonprotected DG. In the other regions studied, the histologic damage was lower or equal in UCP2/3tg animals compared with wt. Consequently, neuroprotection in the thalamus correlated with a high expression of UCP2, which is neuroprotective in a number of models of neurodegenerative diseases.Journal of Cerebral Blood Flow & Metabolism advance online publication, 27 February 2008; doi:10.1038/jcbfm.2008.8.
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| 6. |
- Firsova, Alexandra, et al.
(författare)
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Topographic atlas of cell states identifies regional gene expression in the adult human lung
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Single cell mRNA sequencing of the whole organ has become a popular technique to reveal rare types and subtypes of previously characterized cells as well as to distinguish and characterize gene expression of previously unknown cell types. Unsupervised clustering can reveal tens or even hundreds of variable genes that characterize cell types. Variation in gene expression is often observed within one cell type, and sometimes cannot be biologically explained without mapping of mRNA on tissue. In this study we aim to (i) map the majority of cell types of human lung, (ii) describe variability in their gene expression and (iii) relate this gene expression to cellular location and neighborhoods. Using three different spatial transcriptomics approaches, we mapped epithelial cell states of airways and submucosal gland, and defined cell type-unrelated gene expression variability along proximo-distal axis, including potential regulators and co-regulators of such cell states in the mesenchymal and immune cell niches. In addition, we mapped rare cell types, such as subtypes of neuroendocrine cells, ionocytes and tuft (brush) cells, revealing tracheal preference for ionocytes, and distal airways for GHRL-positive neuroendocrine cells. Finally, we used the created map as a reference for the diseased tissue from patients with stage II COPD and revealed perturbed cell states and COPD-specific imbalance of cell types, affecting immune and AT0 clusters.
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| 7. |
- Flechard, Chris R., et al.
(författare)
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Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 1: Fluxes and budgets of carbon, nitrogen and greenhouse gases from ecosystem monitoring and modelling
- 2020
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 17:6, s. 1583-1620
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Tidskriftsartikel (refereegranskat)abstract
- The impact of atmospheric reactive nitrogen (N-r) deposition on carbon (C) sequestration in soils and biomass of unfertilized, natural, semi-natural and forest ecosystems has been much debated. Many previous results of this dC/dN response were based on changes in carbon stocks from periodical soil and ecosystem inventories, associated with estimates of N-r deposition obtained from large-scale chemical transport models. This study and a companion paper (Flechard et al., 2020) strive to reduce uncertainties of N effects on C sequestration by linking multi-annual gross and net ecosystem productivity estimates from 40 eddy covariance flux towers across Europe to local measurement-based estimates of dry and wet N-r deposition from a dedicated collocated monitoring network. To identify possible ecological drivers and processes affecting the interplay between C and N-r inputs and losses, these data were also combined with in situ flux measurements of NO, N2O and CH4 fluxes; soil NO3- leaching sampling; and results of soil incubation experiments for N and greenhouse gas (GHG) emissions, as well as surveys of available data from online databases and from the literature, together with forest ecosystem (BAS-FOR) modelling. Multi-year averages of net ecosystem productivity (NEP) in forests ranged from -70 to 826 gCm(-2) yr(-1) at total wet + dry inorganic N-r deposition rates (N-dep) of 0.3 to 4.3 gNm(-2) yr(-1) and from -4 to 361 g Cm-2 yr(-1) at N-dep rates of 0.1 to 3.1 gNm(-2) yr(-1) in short semi-natural vegetation (moorlands, wetlands and unfertilized extensively managed grasslands). The GHG budgets of the forests were strongly dominated by CO2 exchange, while CH4 and N2O exchange comprised a larger proportion of the GHG balance in short semi-natural vegetation. Uncertainties in elemental budgets were much larger for nitrogen than carbon, especially at sites with elevated N-dep where N-r leaching losses were also very large, and compounded by the lack of reliable data on organic nitrogen and N-2 losses by denitrification. Nitrogen losses in the form of NO, N2O and especially NO3- were on average 27%(range 6 %-54 %) of N-dep at sites with N-dep < 1 gNm(-2) yr(-1) versus 65% (range 35 %-85 %) for N-dep > 3 gNm(-2) yr(-1). Such large levels of N-r loss likely indicate that different stages of N saturation occurred at a number of sites. The joint analysis of the C and N budgets provided further hints that N saturation could be detected in altered patterns of forest growth. Net ecosystem productivity increased with N-r deposition up to 2-2.5 gNm(-2) yr(-1), with large scatter associated with a wide range in carbon sequestration efficiency (CSE, defined as the NEP/GPP ratio). At elevated N-dep levels (> 2.5 gNm(-2) yr(-1)), where inorganic N-r losses were also increasingly large, NEP levelled off and then decreased. The apparent increase in NEP at low to intermediate N-dep levels was partly the result of geographical cross-correlations between N-dep and climate, indicating that the actual mean dC/dN response at individual sites was significantly lower than would be suggested by a simple, straightforward regression of NEP vs. N-dep.
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| 8. |
- Gulyas, Katalin, et al.
(författare)
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Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis
- 2020
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 39:1, s. 167-175
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesRheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS.Patients and methodsThirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months.ResultsTNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP.ConclusionsAnti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.
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| 9. |
- Horváth, Gábor, et al.
(författare)
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Why do horseflies need polarization vision for host detection? Polarization helps tabanid flies to select sunlit dark host animals from the dark patches of the visual environment
- 2017
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Ingår i: Royal Society Open Science. - : The Royal Society. - 2054-5703. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- Horseflies (Tabanidae) are polarotactic, being attracted to linearly polarized light when searching for water or host animals. Although it is well known that horseflies prefer sunlit dark and strongly polarizing hosts, the reason for this preference is unknown. According to our hypothesis, horseflies use their polarization sensitivity to look for targets with higher degrees of polarization in their optical environment, which as a result facilitates detection of sunlit dark host animals. In this work, we tested this hypothesis. Using imaging polarimetry, we measured the reflection–polarization patterns of a dark host model and a living black cow under various illumination conditions and with different vegetation backgrounds. We focused on the intensity and degree of polarization of light originating from dark patches of vegetation and the dark model/cow. We compared the chances of successful host selection based on either intensity or degree of polarization of the target and the combination of these two parameters. We show that the use of polarization information considerably increases the effectiveness of visual detection of dark host animals even in front of sunny–shady–patchy vegetation. Differentiation between a weakly polarizing, shady (dark) vegetation region and a sunlit, highly polarizing dark host animal increases the efficiency of host search by horseflies.
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| 10. |
- Kish, Laszlo, et al.
(författare)
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Brain : Biological Noise-Based Logic
- 2015
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Ingår i: Advances in Cognitive Neurodynamics (IV). - Dordrecht, Tyskland : Springer Science+Business Media B.V.. - 9789401795487 ; , s. 319-322
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Bokkapitel (refereegranskat)abstract
- Neural spikes in the brain form stochastic sequences, i.e., belong to the class of pulse noises. This stochasticity is a counterintuitive feature because extracting information-such as the commonly supposed neural information of mean spike frequency-requires long times for reasonably low error probability. The mystery could be solved by noise-based logic, wherein randomness has an important function and allows large speed enhancements for special-purpose tasks, and the same mechanism is at work for the brain logic version of this concept.
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