While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth ...and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma‐associated microglia/macrophages (GAMs), on patients’ clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I–IV). Furthermore, we analyzed a cohort of 241 IDH1R132H‐non‐mutant GBM patients for association of GAM subtypes and patient overall survival. Phenotypical properties of GAMs, isolated from high‐grade astrocytomas by CD11b‐based magnetic cell sorting, were analyzed by immunocytochemistry, mRNA microarray, qRT‐PCR and bioinformatic analyses. A higher amount of CD68‐, CD163‐ and CD206‐positive GAMs in the vital tumor core was associated with beneficial patient survival. The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro‐inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti‐inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment. In summary, we present evidence that human GBMs contain mixed M1/M2‐like polarized GAMs and that the levels of different GAM subpopulations in the tumor core are positively associated with overall survival of patients with IDH1R132H‐non‐mutant GBMs.
Dislipidemia is a risk factor for cognitive impairment. We studied the association between interindividual variability of plasma lipids and white matter (WM) microstructure, using diffusion tensor ...imaging (DTI) in 273 healthy adults. Special focus was placed on 7 regions of interest (ROI) which are structural components of cognitive neurocircuitry. We also investigated the effect of plasma lipids on cerebrospinal fluid (CSF) neurofilament light chain (NfL), an axonal degeneration marker. Low density lipoprotein (LDL) and triglyceride (TG) levels showed a negative association with axial diffusivity (AxD) in multiple regions. High density lipoproteins (HDL) showed a positive correlation. The association was independent of Apolipoprotein E (APOE) genotype, blood pressure or use of statins. LDL moderated the relation between NfL and AxD in the body of the corpus callosum (
p
= 0.041), right cingulum gyrus (p = 0.041), right fornix/stria terminalis (
p
= 0.025) and right superior longitudinal fasciculus (
p
= 0.020) and TG in the right inferior longitudinal fasciculus (
p
= 0.004) and left fornix/stria terminalis (
p
= 0.001). We conclude that plasma lipids are associated to WM microstructural changes and axonal degeneration and might represent a risk factor in the transition from healthy aging to disease.
Voltage-gated ion channels are essential for membrane potential maintenance, homeostasis, electrical signal production and controlling the Ca
flow through the membrane. Among all ion channels, the ...key regulators of neuronal excitability are the voltage-gated potassium channels (K
), the largest family of K
channels. Due to the ROS high levels in the aging brain, K
channels might be affected by oxidative agents and be key in aging and neurodegeneration processes. This review provides new insight about channelopathies in the most studied neurodegenerative disorders, such as Alzheimer Disease, Parkinson's Disease, Huntington Disease or Spinocerebellar Ataxia. The main affected K
channels in these neurodegenerative diseases are the K
1, K
2.1, K
3, K
4 and K
7. Moreover, in order to prevent or repair the development of these neurodegenerative diseases, previous K
channel modulators have been proposed as therapeutic targets.
Marchal, P., Andersen, B., Caillart, B., Eigaard, Guyader, O., Hovgaard, H., Iriondo, A., Le Fur, F., Sacchi, J., and Santurtún, M. 2007. Impact of technological creep on fishing effort and fishing ...mortality, for a selection of European fleets–ICES Journal of Marine Science, 64, 192–209. Face-to-face interviews were conducted to identify the main changes in gear and vessel technology that may have improved the fishing efficiency of a number of French, Danish, and Basque fleets over the past few decades. Important changes include the gradual appearance of twin trawls (Danish and French trawlers) and trammel-nets (French gillnetters), and the increased polyvalence of Basque bottom trawlers. The results suggest that fishing effort descriptors that are not traditionally measured (gear type, groundrope type, length of net used per day, headline length, crew size, number of winch or net drums) may have a substantial impact on catch rates. Adjusting fishing effort using such descriptors may generally improve the relationship between fishing effort and fishing mortality.
Abstract Bilingualism as a component of cognitive reserve has been claimed to delay the onset of Alzheimer's disease (AD). However, its effect on cerebrospinal fluid (CSF) AD-biomarkers has not been ...investigated. We assessed cognitive performance and CSF AD-biomarkers, and potential moderation effect of bilingualism on the association between age, CSF AD-biomarkers, and cognition. Cognitively healthy middle-aged participants classified as monolinguals (n = 100, nCSF = 59), early (n = 81, nCSF = 55) and late bilinguals (n = 97, nCSF = 52) were evaluated. Models adjusted for confounders showed that bilinguals performed better than monolinguals on digits backwards (early-bilinguals p = 0.003), Judgment of Line Orientation (JLO) (early-bilinguals p = 0.018; late-bilinguals p = 0.004), and Trail Making Test-B (late-bilinguals p = 0.047). Early bilingualism was associated with lower CSF total-tau ( p = 0.019) and lower prevalence of preclinical AD (NIA-AA classification) ( p = 0.02). Bilingualism showed a moderation effect on the relationship between age and CSF AD-biomarkers and the relationship between age and executive function. We conclude that bilingualism contributes to cognitive reserve enhancing executive and visual-spatial functions. For the first time, this study reveals that early bilingualism is associated with more favorable CSF AD-biomarker profile.
Background
Aging is consistently associated with cortical gray matter (GM) reductions. Bilingualism has been described as a potential reserve contributor for successful brain aging and has been ...associated with a variety of structural changes in cortical morphology. In this study we aim to: 1) Explore differences between bilinguals and monolinguals on the whole brain cortical thickness, area and volume, 2) explore if correlations between age and cortical measures are different between bilinguals and monolinguals, and 3) to evaluate age‐bilingualism interaction effects on the cortical characteristics.
Method
Cross‐sectional study with healthy volunteers from the Gipuzkoa Alzheimer Project (GAP) cohort. Cognitively unimpaired (CDR Global Score = 0) with available 3T MRI were included and classified as bilinguals or monolinguals based on daily use of both Spanish and Basque languages or only Spanish. Subjects with diffuse white matter lesions (Fazekas scale = 3) were excluded. Cortical reconstruction was performed with Freesurfer package v5.1. as described in Montal et al., 2017. Analyses were conducted in the whole brain using linear modeling of the maps and Monte Carlo simulation corrected for multiple comparisons as implemented in FreeSurfer’s QDEC interface.
Result
Sample included 88 bilinguals and 83 monolinguals (see Table 1 for demographic and clinical characteristics). Whole brain cortical thickness, area or volume were not significantly different between groups. Age‐cortical thickness and volume correlation maps showed broader areas of negative associations in the monolingual than in the bilingual group, and inverse associations in the relationship with area characterized by negative correlations in monolinguals and positive and negative correlations in bilinguals (Figure 1). More specifically, significant age‐bilingualism interactions were found for thickness in the right superiorfrontal gyrus (p = 0.012), and for the surface area, in the inferiorparietal (p = 0.0001), supramarginal (p = 0.043) and lingual (p = 0.042) regions of the left hemisphere.
Conclusion
Cortical thickness and area variations occurring in relation to aging in cognitively healthy individuals could be modulated by bilingualism.
•Oxysterols are involved in many biological processes including the regulation of cholesterol homeostasis.•The location of oxysterol metabolising enzymes may play an important role in cellular ...oxysterol concentration.•Oxysterols in biological fluids can use as markers to analyse endogenous flaws in cholesterol/oxysterol homeostasis.
Oxysterols are oxidized derivatives of cholesterol that are formed enzymatically or via reactive oxygen species or both. Cholesterol or oxysterols ingested as food are absorbed and packed into lipoproteins that are taken up by hepatic cells. Within hepatic cells, excess cholesterol is metabolised to form bile acids. The endoplasmic reticulum acts as the main organelle in the bile acid synthesis pathway. Metabolised sterols originating from this pathway are distributed within other organelles and in the cell membrane. The alterations to membrane oxysterol:sterol ratio affects the integrity of the cell membrane. The presence of oxysterols changes membrane fluidity and receptor orientation. It is well documented that hydroxylase enzymes located in mitochondria facilitate oxysterol production via an acidic pathway. More recently, the presence of oxysterols was also reported in lysosomes. Peroxisomal deficiencies favour intracellular oxysterols accumulation. Despite the low abundance of oxysterols compared to cholesterol, the biological actions of oxysterols are numerous and important. Oxysterol levels are implicated in the pathogenesis of multiple diseases ranging from chronic inflammatory diseases (atherosclerosis, Alzheimer’s disease and bowel disease), cancer and numerous neurodegenerative diseases. In this article, we review the distribution of oxysterols in sub-cellular organelles and in biological fluids.
Abstract
Advice for commercially exploited fish stocks is usually given on a stock-by-stock basis. In light of the ecosystem-based fisheries management, the need to move towards a holistic approach ...has been largely acknowledged. In addition, the discard bans in some countries requires consistent catch advice among stocks to mitigate choke species limiting fisheries activity. In this context, in 2015, the European Commission proposed the use of fishing mortality ranges around fishing mortality targets to give flexibility to the catch advice system and improve the use of fishing opportunities in mixed-fisheries. We present a multi-stock harvest control rule (HCR) that uses single stock assessment results and fishing mortality ranges to generate a consistent catch advice among stocks. We tested the performance of the HCR in two different case studies. An artificial case study with three stocks exploited simultaneously by a single fleet and the demersal mixed-fishery operating in Bay of Biscay and Celtic Sea. The HCR produced consistent catch advice among stocks when there was only a single fleet exploiting them. Even more, the HCR removed the impact of the discard ban. However, in a multi-fleet framework the performance of the HCR varied depending on the characteristics of the fleets.
The aim of this research is to provide a comprehensive analysis of the degree of participation and influence of Small-Scale Fisheries (SSF) across the European Union Atlantic Area putting forward a ...set of good practices and recommendations for policymakers, Non-Governmental Organisations and SSF representatives. The actual margin for enhancing the degree of influence of SSF on decision-making processes is still large. Moving towards community-based management models from the current hierarchical models is compulsory. A set of measures have been adopted in Western Waters following participatory processes, introducing self-management and co-management tools at the local and regional levels. This research goes beyond the governance model addressing issues such as the increase of influence when the final decision-makers promote a certain devolution of power to the local/regional levels carried out in parallel with reinforcing the capacity of the SSF representatives to exercise such power.
•The margin for enhancing the influence of SSF on decision-making is still large.•Scarce examples of SSF co-management models available at Western Waters.•High number of organisations representing SSF but low connectivity at Western Waters.•MS to include an SSF Action Plan, EMFF operational programme, including governance.•To enhance the definition of the decision-making rules, guidelines, and timing.
OBJECTIVETo investigate the cognitive profile of healthy individuals with increased Cardiovascular Risk Factors, Aging and Dementia (CAIDE) dementia risk score and to explore whether this association ...is related to vascular burden and CSF biomarkers of amyloidosis and neurodegeneration.
METHODCognitively normal participants (mean age 57.6 years) from the Gipuzkoa Alzheimer Project study were classified as having high risk (HR; n = 82) or low risk (LR; n = 293) for dementia according to a CAIDE score cutoff of 9. Cognitive composites were compared between groups. We explored using generalized linear models the role of APOE genotype, MRI white matter hyperintensities (WMH), and CSF (n = 218) levels of β-amyloid1-42 (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in the association between CAIDE score and cognition.
RESULTSHR participants obtained lower scores on executive function (EF) (p = 0.001) and visual perception and construction (VPC) (p < 0.001) composites. EF composite was associated with CAIDE score × p-tau (p = 0.001), CAIDE score × t-tau (p = 0.001), and WMH (p = 0.003). VPC composite was associated with APOE (p = 0.001), Aβ1–42 (p = 0.004), the interaction APOE × Aβ1–42 (p = 0.003), and WMH (p = 0.004). Performance on global memory was associated with Aβ1–42 (p = 0.006), APOE (p = 0.008), and their interaction (p = 0.006). Analyses were adjusted for age, education, sex, premorbid intelligence, and stress.
CONCLUSIONHealthy participants at increased dementia risk based on CAIDE scores show lower performance in EF and VPC. This difference is related to APOE, WMH, and Alzheimer biomarkers.
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