| 1. |
|
|
| 2. |
- Tiegs, Scott D., et al.
(författare)
-
Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
-
Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
|
|
| 3. |
- Baron, J. S., et al.
(författare)
-
Synthesis Centers as Critical Research Infrastructure
- 2017
-
Ingår i: Bioscience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:8, s. 750-759
-
Tidskriftsartikel (refereegranskat)abstract
- Synthesis centers offer a unique amalgam of culture, infrastructure, leadership, and support that facilitates creative discovery on issues crucial to science and society. The combination of logistical support, postdoctoral or senior fellowships, complex data management, informatics and computing capability or expertise, and most of all, opportunity for group discussion and reflection lowers the "activation energy" necessary to promote creativity and the cross-fertilization of ideas. Synthesis centers are explicitly created and operated as community-oriented infrastructure, with scholarly directions driven by the ever-changing interests and needs of an open and inclusive scientific community. The last decade has seen a rise in the number of synthesis centers globally but also the end of core federal funding for several, challenging the sustainability of the infrastructure for this key research strategy. Here, we present the history and rationale for supporting synthesis centers, integrate insights arising from two decades of experience, and explore the challenges and opportunities for long-term sustainability.
|
|
| 4. |
- Byrne, L. M., et al.
(författare)
-
Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis
- 2017
-
Ingår i: Lancet Neurology. - 1474-4422. ; 16:8, s. 601-609
-
Tidskriftsartikel (refereegranskat)abstract
- Background Blood biomarkers of neuronal damage could facilitate clinical management of and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease. Methods We did a retrospective analysis of healthy controls and carriers of CAG expansion mutations in HTT participating in the 3-year international TRACK-HD study. We studied associations between NfL concentrations in plasma and clinical and MRI neuroimaging findings, namely cognitive function, motor function, and brain volume (global and regional). We used random effects models to analyse cross-sectional associations at each study visit and to assess changes from baseline, with and without adjustment for age and CAG repeat count. In an independent London-based cohort of 37 participants (23 HTT mutation carriers and 14 controls), we further assessed whether concentrations of NfL in plasma correlated with those in CSF. Findings Baseline and follow-up plasma samples were available from 97 controls and 201 individuals carrying HTT mutations. Mean concentrations of NfL in plasma at baseline were significantly higher in HTT mutation carriers than in controls (3.63 [SD 0.54] log pg/mL vs 2.68 [0.52] log pg/mL, p<0.0001) and the difference increased from one disease stage to the next. At any given timepoint, NfL concentrations in plasma correlated with clinical and MRI findings. In longitudinal analyses, baseline NfL concentration in plasma also correlated significantly with subsequent decline in cognition (symbol-digit modality test r=-0.374, p<0.0001; Stroop word reading r=-0.248, p=0.0033), total functional capacity (r=-0.289, p=0.0264), and brain atrophy (caudate r=0.178, p=0.0087; whole-brain r=0602, p<0.0001; grey matter r=0.518, p<00001; white matter r=0.588, p<0.0001; and ventricular expansion r=-0.589, p<0.0001). All changes except Stroop word reading and total functional capacity remained significant after adjustment for age and CAG repeat count. In 104 individuals with premanifest Huntington's disease, NfL concentration in plasma at baseline was associated with subsequent clinical onset during the 3-year follow-up period (hazard ratio 3.29 per log pg/mL, 95% CI 1.48-7.34, p=00036). Concentrations of NfL in CSF and plasma were correlated in mutation carriers (r=0868, p<0.0001). Interpretation NfL in plasma shows promise as a potential prognostic blood biomarker of disease onset and progression in Huntington's disease. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 5. |
- Johnson, Eileanoir B, et al.
(författare)
-
Neurofilament light protein in blood predicts regional atrophy in Huntington disease.
- 2018
-
Ingår i: Neurology. - 1526-632X. ; 90:8
-
Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers.After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression.These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change.
|
|
| 6. |
- Liu, Y., et al.
(författare)
-
Anthropogenic Aerosols Cause Recent Pronounced Weakening of Asian Summer Monsoon Relative to Last Four Centuries
- 2019
-
Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 46:10, s. 5469-5479
-
Tidskriftsartikel (refereegranskat)abstract
- The Asian Summer Monsoon (ASM) affects ecosystems, biodiversity, and food security of billions of people. In recent decades, ASM strength (as represented by precipitation) has been decreasing, but instrumental measurements span only a short period of time. The initiation and the dynamics of the recent trend are unclear. Here for the first time, we use an ensemble of 10 tree ring-width chronologies from the west-central margin of ASM to reconstruct detail of ASM variability back to 1566 CE. The reconstruction captures weak/strong ASM events and also reflects major locust plagues. Notably, we found an unprecedented 80-year trend of decreasing ASM strength within the context of the 448-year reconstruction, which is contrary to what is expected from greenhouse warming. Our coupled climate model shows that increasing anthropogenic sulfate aerosol emissions over the Northern Hemisphere could be the dominant factor contributing to the ASM decrease. Plan Language Summary Monsoonal rainfall has a certain influence on agriculture and industry in the regions of Asian Summer Monsoon (ASM). An understanding of the spatial-temporal variability of the ASM and the associated dynamics is vital for terrestrial ecosystems, water resources, forests, and landscapes. We have developed a 448-year ASM reconstruction back to 1566 CE using 10 tree ring chronologies from the margin region of ASM. We find that historical severe droughts and locust plague disasters during weak ASM events. The recent decreasing ASM trend persisting for over 80 years is unprecedented over the past 448 years. Coupled climate models show that increasing anthropogenic aerosol emissions are the dominant underlying factor. Our aim is that the time series will find a wide range of utility for understanding past climate variability and for predicting future climate change.
|
|
| 7. |
- Liu, Y., et al.
(författare)
-
Recent enhancement of central Pacific El Nino variability relative to last eight centuries
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The far-reaching impacts of central Pacific El Nino events on global climate differ appreciably from those associated with eastern Pacific El Nino events. Central Pacific El Nino events may become more frequent in coming decades as atmospheric greenhouse gas concentrations rise, but the instrumental record of central Pacific sea-surface temperatures is too short to detect potential trends. Here we present an annually resolved reconstruction of NINO4 sea-surface temperature, located in the central equatorial Pacific, based on oxygen isotopic time series from Taiwan tree cellulose that span from 1190 AD to 2007 AD. Our reconstruction indicates that relatively warm Nino4 sea-surface temperature values over the late twentieth century are accompanied by higher levels of interannual variability than observed in other intervals of the 818-year-long reconstruction. Our results imply that anthropogenic greenhouse forcing may be driving an increase in central Pacific El Nino-Southern Oscillation variability and/or its hydrological impacts, consistent with recent modelling studies.
|
|
| 8. |
- Rodrigues, F. B., et al.
(författare)
-
Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease
- 2016
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 139:1, s. 22-25
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre-symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale ’99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme-linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p<0.05. Seventy-six participants were included in this cross-sectional multicenter international pilot study. Age-adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p=0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r=−0.29, p=0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r=0.32, p=0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age-adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. (Figure presented.) In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of neuronal death, in cerebrospinal fluid and found it was increased in patients with Huntington's disease and predicted motor, cognitive, and functional disability in patients. It is therefore likely to be a biomarker of disease progression, and possibly of therapeutic response. Read the Editorial Highlight for this article on page 9. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry
|
|
| 9. |
- Connolly, C, et al.
(författare)
-
Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin
- 2016
-
Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 325, s. 74-88
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's Disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. The YAC128 mouse model of HD expresses the full-length human huntingtin protein with 128 CAG repeats and replicates the phenotype and neurodegeneration that occur in HD. Several studies have implicated a role for neuroinflammation in HD pathogenesis. Studies on presymptomatic HD patients have illustrated microgliosis (activated microglia) in brain regions affected in HD. Mutant huntingtin expressing isolated primary monocytes (human HD patients) and primary macrophages (YAC128) are overactive in response to lipopolysaccharide (LPS) stimulation. In this study we demonstrate that cultured primary microglia (the resident immune cells of the brain cells) from YAC128 mice differentially express a wide number of cytokines compared to wildtype microglia cultures in response to LPS. Furthermore, this study outlines a direct interaction between mutant huntingtin and cytokine secretion in HD microglia. Increased cytokine release in YAC128 microglia can be blocked by cannabinoid activation or by mutant huntingtin knockdown with anti-sense oligonucleotide treatment. Matrix metalloprotease 3 (MMP3), an endogenous neuronal activator of microglia, also induces increased cytokine release from YAC128 microglia compared to wildtype microglia. We found elevated MMP levels in HD CSF, and MMP levels correlate with disease severity in HD. These data support a novel role for MMPs and microglial activation in HD pathogenesis. With an improved understanding of the specific cellular processes involved in HD neuroinflammation, novel therapeutic agents targeting these processes can be developed and hold great promise in the treatment of HD.
|
|
