| 1. |
|
|
| 2. |
|
|
| 3. |
- Underwood, J, et al.
(författare)
-
Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
-
Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
|
|
| 4. |
|
|
| 5. |
- Fornander, Louise, 1984, et al.
(författare)
-
Using nanofluidic channels to probe dynamics of RAD51-Filaments
- 2015
-
Ingår i: 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014. - 9780979806476 ; , s. 1826-1828
-
Konferensbidrag (refereegranskat)abstract
- Using nanochannels, passivated with a lipid bilayer to avoid sticking of proteins, we study Rad51 filaments bound to single- and double stranded DNA. We demonstrate how we can discern different properties of the filaments by studying them at different degrees of confinement. Unlike the bacterial homologue RecA, that forms homogeneous filaments along DNA, Rad51 forms heterogeneous filaments containing both rigid kinks as well as flexible regions. Varying the counterion, the DNA substrate as well as the initial protein concentration, we try to understand the factors governing the structure of the filaments.
|
|
| 6. |
|
|
| 7. |
- Fornander, Louise, 1984, et al.
(författare)
-
Visualizing the Nonhomogeneous Structure of RAD51 Filaments Using Nanofluidic Channels
- 2016
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:33, s. 8403-8412
-
Tidskriftsartikel (refereegranskat)abstract
- RAD51 is the key component of the homologous recombination pathway in eukaryotic cells and performs its task by forming filaments on DNA. In this study we investigate the physical properties of RAD51 filaments formed on DNA using nanofluidic channels and fluorescence microscopy. Contrary to the bacterial ortholog RecA, RAD51 forms inhomogeneous filaments on long DNA in vitro, consisting of several protein patches. We demonstrate that a permanent "kink" in the filament is formed where two patches meet if the stretch of naked DNA between the patches is short. The kinks are readily seen in the present microscopy approach but would be hard to identify using conventional single DNA molecule techniques where the DNA is more stretched. We also demonstrate that protein patches separated by longer stretches of bare DNA roll up on each other and this is visualized as transiently overlapping filaments. RAD51 filaments can be formed at several different conditions, varying the cation (Mg2+ or Ca2+), the DNA substrate (single-stranded or double-stranded), and the RAD51 concentration during filament nucleation, and we compare the properties of the different filaments formed. The results provide important information regarding the physical properties of RAD51 filaments but also demonstrate that nanofluidic channels are perfectly suited to study protein-DNA complexes.
|
|
| 8. |
- Kozik, Nevin P., et al.
(författare)
-
Rapid marine oxygen variability : Driver of the Late Ordovician mass extinction
- 2022
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:46
-
Tidskriftsartikel (refereegranskat)abstract
- The timing and connections between global cooling, marine redox conditions, and biotic turnover are underconstrained for the Late Ordovician. The second most severe mass extinction occurred at the end of the Ordovician period, resulting in ~85% loss of marine species between two extinction pulses. As the only “Big 5” extinction that occurred during icehouse conditions, this interval is an important modern analog to constrain environmental feedbacks. We present a previously unexplored thallium isotope records from two paleobasins that record global marine redox conditions and document two distinct and rapid excursions suggesting vacillating (de)oxygenation. The strong temporal link between these perturbations and extinctions highlights the possibility that dynamic marine oxygen fluctuations, rather than persistent, stable global anoxia, played a major role in driving the extinction. This evidence for rapid oxygen changes leading to mass extinction has important implications for modern deoxygenation and biodiversity declines.
|
|
| 9. |
- Bowman, Chelsie N., et al.
(författare)
-
Integrated sedimentary, biotic, and paleoredox dynamics from multiple localities in southern Laurentia during the late Silurian (Ludfordian) extinction event
- 2020
-
Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 553
-
Tidskriftsartikel (refereegranskat)abstract
- The Silurian was a time of major climatic transition punctuated by multiple biotic crises and global carbon cycle perturbations. The most severe of these biotic events was the late Silurian (Ludfordian) Lau/Kozlowskii extinction event (LKE) and the associated Lau carbon isotope excursion (CIE). Although the extinction event and Lau CIE are globally documented, the only records thus far of local and global marine paleoredox conditions through this interval are from a single region in Scandinavia. Here we examine four sections along a bathymetric transect of mixed carbonate-siliciclastic sediments from western Tennessee, USA. A novel approach using a multi-proxy dataset combining high-resolution geochemical data and microfacies analyses from multiple localities explores the possibilities of local/regional-scale redox heterogeneities during a time of widespread environmental upheaval on a global scale. Paired positive excursions recorded in carbonate carbon isotopes and carbonate-associated sulfate sulfur isotopes support recent work from carbonate and siliciclastic successions from Scandinavia, suggesting a global enhancement of organic carbon and pyrite burial driven by an expansion of euxinic (anoxic and sulfidic water column) conditions in the oceans during the mid-Ludfordian. Furthermore, positive excursions in organic carbon isotopes and pyrite sulfur isotopes reflect the global changes in redox. Stratigraphic trends in I/Ca ratios imply a local expansion of low-oxygen conditions, with low, but non-zero values during the rising limb and peak of the CIE. The fossil assemblages vary across the shelf and through the CIE interval. Stratigraphic changes in fossil assemblages and I/Ca are closely associated with local and global changes in oxygenation and sea level during the mid-Ludfordian. The collective data indicate significant biotic reorganization in response to changes in marine redox conditions and in conjunction with sea-level variation during the LKE interval, but detailed macroscopic biodiversity is currently unconstrained for this region.
|
|
| 10. |
|
|
