A New Approach for Deep Gray Matter Analysis Using Partial-Volume Estimation

Introduction

The existence of partial volume effects in brain MR images makes it challenging to understand physio-pathological alterations underlying signal changes due to pathology across groups of healthy subjects and patients. In this study, we implement a new approach to disentangle gray and white matter alterations in the thalamus and the basal ganglia. The proposed method was applied to a cohort of early multiple sclerosis (MS) patients and healthy subjects to evaluate tissue-specific alterations related to diffuse inflammatory or neurodegenerative processes.

Method

Forty-three relapsing-remitting MS patients and nineteen healthy controls underwent 3T MRI including: (i) fluid-attenuated inversion recovery, double inversion recovery, magnetization-prepared gradient echo for lesion count, and (ii) T1 relaxometry. We applied a partial volume estimation algorithm to T1 relaxometry maps to gray and white matter local concentrations as well as T1 values characteristic of gray and white matter in the thalamus and the basal ganglia. Statistical tests were performed to compare groups in terms of both global T1 values, tissue characteristic T1 values, and tissue concentrations.

Results

Significant increases in global T1 values were observed in the thalamus (p = 0.038) and the putamen (p = 0.026) in RRMS patients compared to HC. In the Thalamus, the T1 increase was associated with a significant increase in gray matter characteristic T1 (p = 0.0016) with no significant effect in white matter.

Conclusion

The presented methodology provides additional information to standard MR signal averaging approaches that holds promise to identify the presence and nature of diffuse pathology in neuro-inflammatory and neurodegenerative diseases.     

PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR

Background

Impaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored.

Methods

Lipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2–4 Patients—The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m²) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m² enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths.

Results

PCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8–4.1] years and 10.0 [7.3–10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results.

Conclusion

In two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function.     

Simulation of Lake Victoria Circulation Patterns Using the Regional Ocean Modeling System (ROMS)

Lake Victoria provides important ecosystem services including transport, water for domestic and industrial uses and fisheries to about 33 million inhabitants in three East African countries. The lake plays an important role in modulating regional climate. Its thermodynamics and hydrodynamics are also influenced by prevailing climatic and weather conditions on diel, seasonal and annual scales. However, information on water temperature and circulation in the lake is limited in space and time. We use a Regional Oceanographic Model System (ROMS) to simulate these processes from 1^st January 2000 to 31^st December 2014. The model is based on real bathymetry, river runoff and atmospheric forcing data using the bulk flux algorithm. Simulations show that the water column exhibits annual cycles of thermo-stratification (September–May) and mixing (June–August). Surface water currents take different patterns ranging from a lake-wide northward flow to gyres that vary in size and number. An under flow exists that leads to the formation of upwelling and downwelling regions. Current velocities are highest at the center of the lake and on the western inshore waters indicating enhanced water circulation in those areas. However, there is little exchange of water between the major gulfs (especially Nyanza) and the open lake, a factor that could be responsible for the different water quality reported in those regions. Findings of the present study enhance understanding of the physical processes (temperature and currents) that have an effect on diel, seasonal, and annual variations in stratification, vertical mixing, inshore—offshore exchanges and fluxes of nutrients that ultimately influence the biotic distribution and trophic structure. For instance information on areas/timing of upwelling and vertical mixing obtained from this study will help predict locations/seasons of high primary production and ultimately fisheries productivity in Lake Victoria.     

Transcriptional profiling of epigenetic regulators in somatic embryos during temperature induced formation of an epigenetic memory in Norway spruce

Planta - A significant number of epigenetic regulators were differentially expressed during embryogenesis at different epitype-inducing conditions. Our results support that methylation of DNA and...     

Midpoint attractors and species richness: Modelling the interaction between environmental drivers and geometric constraints

We introduce a novel framework for conceptualising, quantifying and unifying discordant patterns of species richness along geographical gradients. While not itself explicitly mechanistic, this approach offers a path towards understanding mechanisms. In this study, we focused on the diverse patterns of species richness on mountainsides. We conjectured that elevational range midpoints of species may be drawn towards a single midpoint attractor – a unimodal gradient of environmental favourability. The midpoint attractor interacts with geometric constraints imposed by sea level and the mountaintop to produce taxon‐specific patterns of species richness. We developed a Bayesian simulation model to estimate the location and strength of the midpoint attractor from species occurrence data sampled along mountainsides. We also constructed midpoint predictor models to test whether environmental variables could directly account for the observed patterns of species range midpoints. We challenged these models with 16 elevational data sets, comprising 4500 species of insects, vertebrates and plants. The midpoint predictor models generally failed to predict the pattern of species midpoints. In contrast, the midpoint attractor model closely reproduced empirical spatial patterns of species richness and range midpoints. Gradients of environmental favourability, subject to geometric constraints, may parsimoniously account for elevational and other patterns of species richness.     

Is dietary or microhabitat specialization associated with environmental heterogeneity in horned lizards (Phrynosoma)?

Niche breadth is predicted to correlate with environmental heterogeneity, such that generalists will evolve in heterogeneous environments and specialists will evolve in environments that vary less over space and time. We tested the hypothesis that lizards in a heterogeneous environment were generalists compared to lizards in a homogeneous environment. We compared niche breadths of greater short‐horned lizards by quantifying resource selection in terms of two different niche axes, diet (prey items and trophic level), and microhabitat (ground cover and shade cover) between two populations occurring at different elevations. We assessed the heterogeneity of dietary and microhabitat resources within each population's environment by quantifying the availability of prey items, ground cover, and shade cover in each environment. Overall, our results demonstrate that despite differences in resource heterogeneity between elevations, resource selection did not consistently differ between populations. Moreover, environmental heterogeneity was not associated with generalization of resource use. The low‐elevation site had a broader range of available prey items, yet lizards at the high‐elevation site demonstrated more generalization in diet. In contrast, the high‐elevation site had a broader range of available microhabitats, but the lizard populations at both sites were similarly generalized for shade cover selection and were similarly specialized for ground cover selection. Our results demonstrate that environmental heterogeneity of a particular resource does not necessarily predict the degree to which organisms specialize on that resource.     

SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology

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