Quantifying the role of photoacclimation and self-facilitation for seagrass resilience to light deprivation.

Introduction: Light gradients are ubiquitous in marine systems as light reduces exponentially with depth. Seagrasses have a set of mechanisms that help them to cope with light stress gradients. Physiological photoacclimation and clonal integration help to maximize light capture and minimize carbon losses. These mechanisms can shape plants minimum light requirements (MLR), which establish critical thresholds for seagrass survival and help us predict ecosystem responses to the alarming reduction in light availability. Methods: Using the seagrass Cymodocea nodosa as a case study, we compare the MLR under different carbon model scenarios, which include photoacclimation and/or self-facilitation (based on clonal integration) and that where parameterized with values from field experiments. Results: Physiological photoacclimation conferred plants with increased tolerance to reducing light, approximately halving their MLR from 5-6% surface irradiance (SI) to ≈ 3% SI. In oligotrophic waters, this change in MLR could translate to an increase of several meters in their depth colonization limit. In addition, we show that reduced mortality rates derived from self-facilitation mechanisms (promoted by high biomass) induce bistability of seagrass meadows along the light stress gradient, leading to abrupt shifts and hysteretic behaviors at their deep limit. Discussion: The results from our models point to (i) the critical role of physiological photoacclimation in conferring greater resistance and ability to recover (i.e., resilience), to seagrasses facing light deprivation and (ii) the importance of self-facilitating reinforcing mechanisms in driving the resilience and recovery of seagrass systems exposed to severe light reduction events.

Nutrient conditions determine the strength of herbivore-mediated stabilizing feedbacks in barrens.

Abiotic environmental conditions can significantly influence the way species interact. In particular, plant-herbivore interactions can be substantially dependent on temperature and nutrients. The overall product of these relationships is critical for the fate and stability of vegetated ecosystems like marine forests. The last few decades have seen a rapid spread of barrens on temperate rocky reefs mainly as a result of overgrazing. The ecological feedbacks that characterize the barren state involve a different set of interactions than those occurring in vegetated habitats. Reversing these trends requires a proper understanding of the novel feedbacks and the conditions under which they operate. Here, we explored the role of a secondary herbivore in reinforcing the stability of barrens formed by sea urchin overgrazing under different nutrient conditions. Combining comparative and experimental studies in two Mediterranean regions characterized by contrasting nutrient conditions, we assessed: (i) if the creation of barren areas enhances limpet abundance, (ii) the size-specific grazing impact by limpets, and (iii) the ability of limpets alone to maintain barrens. Our results show that urchin overgrazing enhanced limpet abundance. The effects of limpet grazing varied with nutrient conditions, being up to five times more intense under oligotrophic conditions. Limpets were able to maintain barrens in the absence of sea urchins only under low-nutrient conditions, enhancing the stability of the depauperate state. Overall, our study suggests a greater vulnerability of subtidal forests in oligotrophic regions of the Mediterranean and demonstrates the importance of environment conditions in regulating feedbacks mediated by plant-herbivore interactions.

Understanding the depth limit of the seagrass Cymodocea nodosa as a critical transition: Field and modeling evidence.

Changes in light and sediment conditions can sometimes trigger abrupt regime shifts in seagrass meadows resulting in dramatic and unexpected die-offs of seagrass. Light attenuates rapidly with depth, and in seagrass systems with non-linear behaviours, can serve as a sharp boundary beyond which the meadow transitions to bare sand. Determining system behaviour is therefore essential to ensuring resilience is maintained and to prevent stubborn critical ecosystem transitions caused by declines in water quality. Here we combined field and modelling studies to explore the transition from meadow to bare sand in the seagrass Cymodocea nodosa at the limit of its depth distribution in a shallow, light-limited bay. We first describe the relationship between light availability and seagrass density along a depth gradient in an extensive unfragmented meadow (Alfacs bay, NE Spain). We then develop a simple mechanistic model to characterise system behaviour. In the field, we identified sharp decline in shoot density beyond a threshold of ∼1.9 m depth, shifting from a vegetated state to bare sand. The dynamic population model we developed assumes light-dependent growth and an inverse density-dependent mortality due to facilitation between shoots (mortality rate decreases as shoot density increases). The model closely tracked our empirical observations, and both the model and the field data showed signs of bistability. This strongly suggests that the depth limit of C. nodosa is a critical transition driven by photosynthetic light requirements. While the mechanisms still need to be confirmed with experimental evidence, recognizing the non-linear behaviour of C. nodosa meadows is vital not only in improving our understanding of light effects on seagrass dynamics, but also in managing shallow-water meadows. Given the shallow threshold (<2m), light-limited systems may experience significant and recalcitrant meadow retractions with even small changes in sediment and light conditions. Understanding the processes underlying meadow resilience can inform the maintenance and restoration of meadows worldwide.

Activating cannabinoid receptor 2 preserves axonal health through GSK-3ß/NRF2 axis in adrenoleukodystrophy.

Aberrant endocannabinoid signaling accompanies several neurodegenerative disorders, including multiple sclerosis. Here, we report altered endocannabinoid signaling in X-linked adrenoleukodystrophy (X-ALD), a rare neurometabolic demyelinating syndrome caused by malfunction of the peroxisomal ABCD1 transporter, resulting in the accumulation of very long-chain fatty acids (VLCFAs). We found abnormal levels of cannabinoid receptor 2 (CB2r) and related endocannabinoid enzymes in the brain and peripheral blood mononuclear cells (PBMCs) of X-ALD patients and in the spinal cord of a murine model of X-ALD. Preclinical treatment with a selective agonist of CB2r (JWH133) halted axonal degeneration and associated locomotor deficits, along with normalization of microgliosis. Moreover, the drug improved the main metabolic disturbances underlying this model, particularly in redox and lipid homeostatic pathways, including increased lipid droplets in motor neurons, through the modulation of the GSK-3ß/NRF2 axis. JWH133 inhibited Reactive Oxygen Species elicited by excess VLCFAs in primary microglial cultures of Abcd1-null mice. Furthermore, we uncovered intertwined redox and CB2r signaling in the murine spinal cords and in patient PBMC samples obtained from a phase II clinical trial with antioxidants (NCT01495260). These findings highlight CB2r signaling as a potential therapeutic target for X-ALD and perhaps other neurodegenerative disorders that present with dysregulated redox and lipid homeostasis.

An integrated assessment of the Good Environmental Status of Mediterranean Marine Protected Areas.

Local, regional and global targets have been set to halt marine biodiversity loss. Europe has set its own policy targets to achieve Good Environmental Status (GES) of marine ecosystems by implementing the Marine Strategy Framework Directive (MSFD) across member states. We combined an extensive dataset across five Mediterranean ecoregions including 26 Marine Protected Areas (MPAs), their reference unprotected areas, and a no-trawl case study. Our aim was to assess if MPAs reach GES, if their effects are local or can be detected at ecoregion level or up to a Mediterranean scale, and which are the ecosystem components driving GES achievement. This was undertaken by using the analytical tool NEAT (Nested Environmental status Assessment Tool), which allows an integrated assessment of the status of marine systems. We adopted an ecosystem approach by integrating data from several ecosystem components: the seagrass Posidonia oceanica, macroalgae, sea urchins and fish. Thresholds to define the GES were set by dedicated workshops and literature review. In the Western Mediterranean, most MPAs are in good/high status, with P. oceanica and fish driving this result within MPAs. However, GES is achieved only at a local level, and the Mediterranean Sea, as a whole, results in a moderate environmental status. Macroalgal forests are overall in bad condition, confirming their status at risk. The results are significantly affected by the assumption that discrete observations over small spatial scales are representative of the total extension investigated. This calls for large-scale, dedicated assessments to realistically detect environmental status changes under different conditions. Understanding MPAs effectiveness in reaching GES is crucial to assess their role as sentinel observatories of marine systems. MPAs and trawling bans can locally contribute to the attainment of GES and to the fulfillment of the MSFD objectives. Building confidence in setting thresholds between GES and non-GES, investing in long-term monitoring, increasing the spatial extent of sampling areas, rethinking and broadening the scope of complementary tools of protection (e.g., Natura 2000 Sites), are indicated as solutions to ameliorate the status of the basin.

Resilience of seagrass populations to thermal stress does not reflect regional differences in ocean climate.

The prevalence of local adaptation and phenotypic plasticity among populations is critical to accurately predicting when and where climate change impacts will occur. Currently, comparisons of thermal performance between populations are untested for most marine species or overlooked by models predicting the thermal sensitivity of species to extirpation. Here we compared the ecological response and recovery of seagrass populations (Posidonia oceanica) to thermal stress throughout a year-long translocation experiment across a 2800-km gradient in ocean climate. Transplants in central and warm-edge locations experienced temperatures > 29°C, representing thermal anomalies > 5°C above long-term maxima for cool-edge populations, 1.5°C for central and < 1°C for warm-edge populations. Cool-edge, central and warm-edge populations differed in thermal performance when grown under common conditions, but patterns contrasted with expectations based on thermal geography. Cool-edge populations did not differ from warm-edge populations under common conditions and performed significantly better than central populations in growth and survival. Our findings reveal that thermal performance does not necessarily reflect the thermal geography of a species. We demonstrate that warm-edge populations can be less sensitive to thermal stress than cooler, central populations suggesting that Mediterranean seagrasses have greater resilience to warming than current paradigms suggest.

Sublethal effects of a rapidly spreading native alga on a key herbivore.

Multiple anthropogenic stressors are causing a global decline in foundation species, including macrophytes, often resulting in the expansion of functionally different, more stressor-tolerant macrophytes. Previously subdominant species may experience further positive demographic feedback if they are exposed to weaker plant-herbivore interactions, possibly via decreased palatability or being structurally different from the species they are replacing. However, the consequences of the spread of opportunistic macrophytes for the local distribution and life history of herbivores are unknown.The green alga, Caulerpa filiformis, previously a subdominant macrophyte on low intertidal-shallow subtidal rock shores, is becoming locally more abundant and has spread into warmer waters across the coast of New South Wales, Australia.In this study, we measured (a) the distribution and abundance of a key consumer, the sea urchin Heliocidaris erythrogramma, across a seascape at sites where C. filiformis has become dominant, (b) performed behavioral field experiments to test the role of habitat selection in determining the local distribution of H. erythrogramma, and (c) consumer experiments to test differential palatability between previously dominant higher quality species like Ecklonia radiata and Sargassum sp. and C. filiformis and the physiological consequences of consuming it.At all sites, urchin densities were positively correlated with distance away from C. filiformis beds, and they actively moved away from beds. Feeding experiments showed that, while urchins consumed C. filiformis, sometimes in equal amounts to higher quality algae, there were strong sublethal consequences associated with C. filiformis consumption, mainly on reproductive potential (gonad size). Specifically, the gonad size of urchins that fed on C. filiformis was equivalent to that in starved urchins. There was also a tendency for urchin mortality to be greater when fed C. filiformis.Overall, strong negative effects on herbivore life-history traits and potentially their survivorship may establish further positive feedback on C. filiformis abundance that contributes to its spread and may mediate shifts from top-down to bottom-up control at locations where C. filiformis has become dominant.

Homogenization and miniaturization of habitat structure in temperate marine forests.

Humans are rapidly transforming the structural configuration of the planet's ecosystems, but these changes and their ecological consequences remain poorly quantified in underwater habitats. Here, we show that the loss of forest-forming seaweeds and the rise of ground-covering 'turfs' across four continents consistently resulted in the miniaturization of underwater habitat structure, with seascapes converging towards flattened habitats with smaller habitable spaces. Globally, turf seascapes occupied a smaller architectural trait space and were structurally more similar across regions than marine forests, evidencing habitat homogenization. Surprisingly, such habitat convergence occurred despite turf seascapes consisting of vastly different species richness and with different taxa providing habitat architecture, as well as across disparate drivers of marine forest decline. Turf seascapes contained high sediment loads, with the miniaturization of habitat across 100s of km in mid-Western Australia resulting in reefs retaining an additional ~242 million tons of sediment (four orders of magnitude more than the sediments delivered fluvially annually). Together, this work demonstrates that the replacement of marine forests by turfs is a generalizable phenomenon that has profound consequences for the ecology of temperate reefs.

Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study.

Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and age-matched controls. Lipidomic profiles of this subcellular fraction were obtained using liquid chromatography and mass spectrometry. We validated the mechanisms behind presumable lipidomic changes by exploring ALS surrogate models including human motor neurons (derived from ALS lines and controls) subjected to oxidative stress, the hSOD-G93A transgenic mice, and samples from an independent cohort of ALS patients. Among the differential lipid species, we noted 41 potential identities, mostly belonging to phospholipids (particularly ether phospholipids, as plasmalogens), as well as diacylglycerols and triacylglycerides. Decreased expression of alkyldihydroxyacetonephosphate synthase (AGPS)-a critical peroxisomal enzyme in plasmalogen synthesis-is found in motor neuron disease models; this occurs in parallel with an increase in the expression of sterol carrier protein 2 (SCP2) mRNA in ALS and Scp2 levels in G93A transgenic mice. Further, we identified diminished expression of diacylglycerol-related enzymes, such as phospholipase C ßI (PLCßI) and protein kinase CßII (PKCßII), linked to diacylglycerol metabolism. Finally, lipid droplets were recognized in the nuclei, supporting the identification of triacylglycerides as differential lipids. Our results point to the potentially pathogenic role of altered composition of nuclear membrane lipids and lipids in the nucleoplasm in the anterior horn of the spinal cord in ALS. Overall, these data support the usefulness of subcellular lipidomics applied to neurodegenerative diseases.

Gender-Specific Beneficial Effects of Docosahexaenoic Acid Dietary Supplementation in G93A-SOD1 Amyotrophic Lateral Sclerosis Mice.

Docosahexaenoic acid (DHA) is an essential fatty acid modulating key nervous system functions, including neuroinflammation, and regulation of pre- and postsynaptic membrane formation. DHA concentration decreases in the lumbar spinal cord (LSC) of amyotrophic lateral sclerosis (ALS) patients and murine preclinical models. Using a dietary supplementation, we increased DHA levels (2% mean increase, p < 0.01) in the LSC of the familial ALS murine model B6SJL-Tg(SOD1*G93A)1Gur/J. This DHA-enriched diet significantly increases male mouse survival by 7% (average 10 days over 130 days of life expectancy), and delays motor dysfunction (based on stride length) and transgene-associated weight loss (p < 0.01). DHA supplementation led to an increased anti-inflammatory fatty acid profile (ca 30%, p < 0.01) and a lower concentration of circulating proinflammatory cytokine TNF-α (p < 0.001 in males). Furthermore, although DHA-treated mice did not exhibit generally decreased protein oxidative markers (glutamic and aminoadipic semialdehydes, carboxyethyllysine, carboxymethyllysine, and malondialdehydelysine), dietary intake of DHA reduced immunoreactivity towards DNA oxidative damage markers (8-oxo-dG) in the LSC. In vitro we demonstrate that DHA and α-tocopherol addition to a model of motor neuron demise (neonatal rat organotypic spinal cord model under chronic excitotoxicity) also preserves motor neuron number, in comparison with untreated spinal cords. Also, beneficial effects on cell viability were evidenced for the motor neuron cell line NSC-34 in front of H2O2 insult (p < 0.001). Globally we show a sex-specific benefit of dietary DHA supplementation in the G93A ALS mouse model, compared with mice fed an isocaloric control or a n-3-depleted diet. These changes were associated with an increased DHA concentration in the LSC and were compatible with in vitro results showing DHA neuroprotective properties. These results suggest the need for further study on the interaction of gender-influenced biological parameters and DHA in ALS pathogenesis.

Impairment of Mitochondrial Redox Status in Peripheral Lymphocytes of Multiple Sclerosis Patients.

Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted [n = 58: 34 MS and 24 healthy subjects (control group)]. We have measured superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041, respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative protein content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044, and p = 0.051, respectively), which was maintained for complexes I, III, and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend toward increased plasma lactate concentration was detected [8.04 mg lactate/dL (5.25, 9.49) in the control group, 11.36 mg lactate/dL (5.41, 14.81) in MS patients] that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for the first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level.

Consumptive and non-consumptive effects of predators vary with the ontogeny of their prey.

Predators exert a strong influence on ecological communities by reducing the abundance of prey (consumptive effects) and shaping their foraging behavior (non-consumptive effects). Although the prevalence of trophic cascades triggered by non-consumptive effects is increasingly recognized in a wide range of ecosystems, how its relative strength changes as prey individuals grow in size along various life stages remains poorly resolved. We investigated how the effects of predators vary with the ontogeny of a key herbivorous sea urchin, which is responsible for transforming diverse macroalgal forests to a barren state dominated by bare rock and encrusting coralline algae. We conducted a series of field and laboratory experiments to determine how susceptibility to predation, prey behavioral responses, and grazing impact on algal cover vary with sea urchin size. The consumptive effects of predators were greater on smaller sea urchin size classes, which were more susceptible to predation. Unexpectedly however, predator non-consumptive effects acted only on larger sea urchins, significantly reducing their grazing activity in the presence of predator cues. Crucially, only these larger sea urchins were capable of overgrazing macroalgae in the field, with non-consumptive effects reducing sea urchin foraging activity and macroalgal grazing impact by 60%. The decoupling between risk and fear as prey grow indicates that the strength of consumptive and non-consumptive trophic cascades may act differently at different ontogenetic stages of prey. While the consumptive effects of predators directly influence population numbers, the consequences of non-consumptive effects may far outlive consumptive effects as prey grow, finding refuge in size, but not from fear.

The richness of small pockets: Decapod species peak in small seagrass patches where fish predators are absent.

Patchy landscapes behave differently from continuous ones. Patch size can influence species behaviour, movement, feeding and predation rates, with flow-on consequences for the diversity of species that inhabit these patches. To understand the importance of patchiness on regional species pools, we measured decapod richness and abundance in several seagrass patches with contrasting sizes. Additionally, we evaluated potential drivers of patch-specific species distribution including resource abundance, predator habitat use and the structural complexity of patches. Our results showed a non-random distribution of decapod species: small patches were clear hotspots of diversity and abundance, particularly of larger-bodied epifaunal decapods. Interestingly, these hotspots were characterized by lower nutrient resources, lower canopy height, but also lower predator use. Small fish invertivores such as Coris julis and several species of Symphodus were mostly restricted to large patches. These resident predators may be critical in clumping predation in large patches with consequences for how biodiversity of their prey is distributed across the seascape. Our results highlight the idea that a habitat mosaic with both large and small seagrass patches would potentially bolster biodiversity because preys and predators may seek refuge in patches of different sizes.

Cryptic exon splicing function of TARDBP interacts with autophagy in nervous tissue.

TARDBP (TAR DNA binding protein) is one of the components of neuronal aggregates in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We have developed a simple quantitative method to evaluate TARDBP splicing function that was applied to spinal cord, brainstem, motor cortex, and occipital cortex in ALS (n = 8) cases compared to age- and gender-matched control (n = 17). Then, we quantified the abundance of a TARDBP-spliced cryptic exon present in ATG4B (autophagy related 4B cysteine peptidase) mRNA. Results of these analyses demonstrated that the loss of this TARDBP function in spinal cord, brainstem, motor cortex, and occipital cortex differentiated ALS from controls (area under the curve of receiver operating characteristic: 0.85). Significant correlations were also observed between cryptic exon levels, age, disease duration, and aberrant mRNA levels. To test if TARDBP function in splicing is relevant in ATG4B major function (autophagy) we downregulated TARDBP expression in human neural tissue and in HeLa cells, demonstrating that TARDBP is required for maintaining the expression of ATG4B. Further, ATG4B overexpression alone is sufficient to completely prevent the increase of SQSTM1 induced by TARDBP downregulation in human neural tissue cells and in cell lines. In conclusion, the present findings demonstrate abnormal alternative splicing of ATG4B transcripts in ALS neural tissue in agreement with TARDBP loss of function, leading to impaired autophagy. ABBREVIATIONS: ALS: amyotrophic lateral sclerosis; ATG4B: autophagy related 4B cysteine peptidase; AUC: area under the curve; FTLD: frontotemporal lobar degeneration; iPSC: induced pluripotent stem cells; ROC: receiver operating characteristic; TARDBP: TAR DNA binding protein; RT-qPCR: quantitative RT-PCR.

Contrasting effects of ocean warming on different components of plant-herbivore interactions.

There is increasing uncertainty of how marine ecosystems will respond to rising temperatures. While studies have focused on the impacts of warming on individual species, knowledge of how species interactions are likely to respond is scant. The strength of even simple two-species interactions is influenced by several interacting mechanisms, each potentially changing with temperature. We used controlled experiments to assess how plant-herbivore interactions respond to temperature for three structural dominant macrophytes in the Mediterranean and their principal sea urchin herbivore. Increasing temperature differentially influenced plant-specific growth, sea urchin growth and metabolism, consumption rates and herbivore preferences, but not movement behaviour. Evaluating these empirical observations against conceptual models of plant-herbivore performance, it appears likely that while the strength of herbivory may increase for the tested macroalga, for the two dominant seagrasses, the interaction strength may remain relatively unchanged or even weaken as temperatures rise. These results show a clear set of winners and losers in the warming Mediterranean as the complex factors driving species interactions change.

Immanent conditions determine imminent collapses: nutrient regimes define the resilience of macroalgal communities.

Predicting where state-changing thresholds lie can be inherently complex in ecosystems characterized by nonlinear dynamics. Unpacking the mechanisms underlying these transitions can help considerably reduce this unpredictability. We used empirical observations, field and laboratory experiments, and mathematical models to examine how differences in nutrient regimes mediate the capacity of macrophyte communities to sustain sea urchin grazing. In relatively nutrient-rich conditions, macrophyte systems were more resilient to grazing, shifting to barrens beyond 1 800 g m-2 (urchin biomass), more than twice the threshold of nutrient-poor conditions. The mechanisms driving these differences are linked to how nutrients mediate urchin foraging and algal growth: controlled experiments showed that low-nutrient regimes trigger compensatory feeding and reduce plant growth, mechanisms supported by our consumer-resource model. These mechanisms act together to halve macrophyte community resilience. Our study demonstrates that by mediating the underlying drivers, inherent conditions can strongly influence the buffer capacity of nonlinear systems.

Adipocyte lipopolysaccharide binding protein (LBP) is linked to a specific lipidomic signature.

OBJECTIVE: Lipopolysaccharide binding protein (LBP) is part of a family of structurally and functionally related lipid transfer proteins. This study aimed to investigate the associations of LBP with the lipid composition of human adipose tissue. METHODS: Lipidomic analysis was performed in whole adipose tissue. To validate the associations found, LBP was knocked down (KD) in 3T3-L1 adipocytes, and lipidomic profile was evaluated by nontargeted lipidomics. RESULTS: LBP gene expression was negatively associated with phosphatidylcholine, phosphatidylserine, and sphingomyelin relative abundance in vivo. LBP expression was also decreased in those samples with the highest docosahexanoic content, implicated in the resolution of inflammation. The KD of LBP (by ∼70%) led to sharp changes in the lipidome of adipocytes. Of note, specific plasmalogen species PE(O-16:0/22:5), PE(38:2), odd chain glycerolipids, and cholesteryl linoleate were upregulated by LBP KD. In contrast, GM3 gangliosides, several ceramides, a triacylglycerol potentially containing arachidonate, and cholesteryl palmitate were downregulated by LBP KD. CONCLUSIONS: LBP seems to play a role in the regulation of lipid composition of adipose tissue linked to resilience to inflammation.

Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis.

BACKGROUND: Docosahexaenoic acid (DHA), a key lipid in nervous system homeostasis, is depleted in the spinal cord of sporadic amyotrophic lateral sclerosis (sALS) patients. However, the basis for such loss was unknown. METHODS: DHA synthetic machinery was evaluated in spinal cord samples from ALS patients and controls by immunohistochemistry and western blot. Further, lipid composition was measured in organotypic spinal cord cultures by gas chromatography and liquid chromatography coupled to mass spectrometry. In these samples, mitochondrial respiratory functions were measured by high resolution respirometry. Finally, Neuro2-A and stem cell-derived human neurons were used for evaluating mechanistic relationships between TDP-43 aggregation, oxidative stress and cellular changes in DHA-related proteins. RESULTS: ALS is associated to changes in the spinal cord distribution of DHA synthesis enzymatic machinery comparing ten ALS cases and eight controls. We found increased levels of desaturases (ca 95% increase, p<0.001), but decreased amounts of DHA-related ß-oxidation enzymes in ALS samples (40% decrease, p<0.05). Further, drebrin, a DHA-dependent synaptic protein, is depleted in spinal cord samples from ALS patients (around 40% loss, p<0.05). In contrast, chronic excitotoxicity in spinal cord increases DHA acid amount, with both enhanced concentrations of neuroprotective docosahexaenoic acid-derived resolvin D, and higher lipid peroxidation-derived molecules such as 8-iso-prostaglandin-F2-α (8-iso-PGF2α) levels. Since α-tocopherol improved mitochondrial respiratory function and motor neuron survival in these conditions, it is suggested that oxidative stress could boost motor neuron loss. Cell culture and metabolic flux experiments, showing enhanced expression of desaturases (FADS2) and ß-oxidation enzymes after H2O2 challenge suggest that DHA production can be an initial response to oxidative stress, driven by TDP-43 aggregation and drebrin loss. Interestingly, these changes were dependent on cell type used, since human neurons exhibited losses of FADS2 and drebrin after oxidative stress. These features (drebrin loss and FADS2 alterations) were also produced by transfection by aggregation prone C-terminal fragments of TDP-43. CONCLUSIONS: sALS is associated with tissue-specific DHA-dependent synthetic machinery alteration. Furthermore, excitotoxicity sinergizes with oxidative stress to increase DHA levels, which could act as a response over stress, involving the expression of DHA synthetic enzymes. Later on, this allostatic overload could exacerbate cell stress by contributing to TDP-43 aggregation. This, at its turn, could blunt this protective response, overall leading to DHA depletion and neuronal dysfunction.

Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a gender bias towards major prevalence in male individuals. Several data suggest the involvement of oxidative stress and mitochondrial dysfunction in its pathogenesis, though differences between genders have not been evaluated. For this reason, we analysed features of mitochondrial oxidative metabolism, as well as mitochondrial chain complex enzyme activities and protein expression, lipid profile, and protein oxidative stress markers, in the Cu,Zn superoxide dismutase with the G93A mutation (hSOD1-G93A)- transgenic mice and Neuro2A(N2A) cells overexpressing hSOD1-G93A. RESULTS AND CONCLUSIONS: Our results show that overexpression of hSOD1-G93A in transgenic mice decreased efficiency of mitochondrial oxidative phosphorylation, located at complex I, revealing a temporal delay in females with respect to males associated with a parallel increase in selected markers of protein oxidative damage. Further, females exhibit a fatty acid profile with higher levels of docosahexaenoic acid at 30 days. Mechanistic studies showed that hSOD1-G93A overexpression in N2A cells reduced complex I function, a defect prevented by 17ß-estradiol pretreatment. In conclusion, ALS-associated SOD1 mutation leads to delayed mitochondrial dysfunction in female mice in comparison with males, in part attributable to the higher oestrogen levels of the former. This study is important in the effort to further understanding of whether different degrees of spinal cord mitochondrial dysfunction could be disease modifiers in ALS.

Do primary health centres and hospitals contribute equally towards achievement of the transversal clinical competencies of medical students? Performance on the Objective Structured Clinical Examination (OSCE) in competency acquisition / ¿Obtienen los mismos resultados en las competencias transversales los alumnos de Medicina que realizan sus prácticas en la Atención Primaria que en el hospital? Análisis de la adquisición de competencias mediante una Evaluación de Competencias Objetiva y Estructurada (ECOE)

OBJECTIVES: The adaptation of the educational programmes of European faculties of medicine to the European Higher Education Area guidelines has focused curricula design on competence acquisition.competencies are defined as the achievements of a predetermined level of efficacy in real-world scenarios. Our objective was to assess whether performance on a common competence evaluation test, the Objective Structured Clinical Examination (OSCE), resulted in different scores for second-year students after a practical medical training course took place in a primary health centre (PHC) or in a hospital. DESIGN: A descriptive study was conducted during the 2010-2014 academic year of the OSCE test scores obtained by all second-year students. LOCATION: Faculty of Medicine at the University of Lleida (Catalonia, Spain). MAIN MEASUREMENTS: We performed a correlation analysis between students who completed their practical medical training at the PHC and hospitals utilising Student's t-test for comparison of means. RESULTS: 423 students who completed internships at the PHC and at hospitals obtained OSCE mean scores of 7.32 (SD; IC) (0.82; 7.18-7.47) points and 7.17 (0.83; 6.07-7.26) points, respectively (p = 0.07). CONCLUSIONS: Second-year medical students acquired similar competency levels in the two analysed training scenarios. The two areas both serve their teaching purpose

OBJECTIVES: The adaptation of the educational programmes of European faculties of medicine to the European Higher Education Area guidelines has focused curricula design on competence acquisition.competencies are defined as the achievements of a predetermined level of efficacy in real-world scenarios. Our objective was to assess whether performance on a common competence evaluation test, the Objective Structured Clinical Examination (OSCE), resulted in different scores for second-year students after a practical medical training course took place in a primary health centre (PHC) or in a hospital. DESIGN: A descriptive study was conducted during the 2010-2014 academic year of the OSCE test scores obtained by all second-year students. LOCATION: Faculty of Medicine at the University of Lleida (Catalonia, Spain). MAIN MEASUREMENTS: We performed a correlation analysis between students who completed their practical medical training at the PHC and hospitals utilising Student's t-test for comparison of means. RESULTS: 423 students who completed internships at the PHC and at hospitals obtained OSCE mean scores of 7.32 (SD; IC) (0.82; 7.18-7.47) points and 7.17 (0.83; 6.07-7.26) points, respectively (p = 0.07). CONCLUSIONS: Second-year medical students acquired similar competency levels in the two analysed training scenarios. The two areas both serve their teaching purpose