Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are ...associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging. Main changes affect levels of plasmalogens, polyunsaturated fatty acids (especially docosahexaenoic acid and arachidonic acid), total polar lipids (mainly phosphatidylinositol, sphingomyelin, sulfatides, and cerebrosides), and total neutral lipids (particularly cholesterol and sterol esters). Besides, relevant relationships between main fatty acids and/or lipid classes were altered in an age-related manner. This “lipid raft aging” exhibits clear gender differences and appear to be more pronounced in women than in men, especially in older (postmenopausal) women. The outcomes led us to conclude that human cortical lipid rafts are modified by aging in a gender-dependent fashion. Given the central role of bilayer lipid matrix in lipid rafts functionality and neuronal signaling, we hypothesize that these findings might underlie the higher prevalence of cognitive decline evolving toward Alzheimer's disease in postmenopausal women.
•Lithium production and related-technology generation are two different processes.•Asymmetries between lithium producers and technology creators are notable.•Knowledge generation within the GVCLB is ...concentrated into just five economies.•Scarce knowledge connectivity at the international level characterizes the GVCLB.•Significant international divergence between technological and commercial advantages.
The Global Value Chain (GVC) literature generally highlights the opportunities for developing economies to be found in technological upgrading – although the generation of technology tends to be associated with the highest added-value stages, what could be a limiting aspect in those chains based primarily on natural resources. The case of lithium batteries allows analysis of the trade-off between technology generation and international collaboration, as well as any potential asymmetries between producers of natural resources and end-use products within the same GVC. Lithium is a relevant component, currently seen as a valuable player in the reduction of fossil fuel emissions, given the potential of lithium batteries for energy storage, in final applications ranging from consumer electronics to electric vehicles. Our findings show a divergent relationship between lithium producers and related technologies at the country level, across the different stages of the Global Value Chain for Lithium Batteries (GVCLB), and this suggests that upgrading throughout the value chain could foster imbalances. Empirical analysis has been conducted using data from patent applications made to the European Patent Office, and the findings reveal wide international divergence and numerous interactions within the GVCLB, defining a complex international pattern of collaboration, with technology generation concentrated into very few economies.
Lipids in the brain are major components playing structural functions as well as physiological roles in nerve cells, such as neural communication, neurogenesis, synaptic transmission, signal ...transduction, membrane compartmentalization, and regulation of gene expression. Determination of brain lipid composition may provide not only essential information about normal brain functioning, but also about changes with aging and diseases. Indeed, deregulations of specific lipid classes and lipid homeostasis have been demonstrated in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, recent studies have shown that membrane microdomains, named lipid rafts, may change their composition in correlation with neuronal impairment. Lipid rafts are key factors for signaling processes for cellular responses. Lipid alteration in these signaling platforms may correlate with abnormal protein distribution and aggregation, toxic cell signaling, and other neuropathological events related with these diseases. This review highlights the manner lipid changes in lipid rafts may participate in the modulation of neuropathological events related to AD and PD. Understanding and characterizing these changes may contribute to the development of novel and specific diagnostic and prognostic biomarkers in routinely clinical practice.
Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein-lipid and protein-protein ...interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson's disease (PD) and incidental Parkinson's disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders.
Universities are relevant actors in research and development (R&D) and, increasingly, in innovation. These institutions play a significant role in the generation and transfer of scientific and ...technical knowledge. They may also adopt an orchestration role, in order to combine diverse national and international sources of knowledge through collaboration networks that can enhance their ability to transfer it to industry and society. In this paper, we seek to demonstrate that, if this pattern is confirmed, larger benefits can be achieved and translated into better performance and greater impacts on the development of local innovation ecosystems. Using data on patents granted to universities by the United States Patent and Trademark Office (USPTO) from 1990 to 2017, we study the technological performance of Spanish universities to illustrate how collaboration patterns affect the relative impact on their innovative activities. Our contribution identifies a dual complementary and geographically dispersed pattern of collaboration in the evolution of universities' technological performance, while the existence of public-private partnerships and the generation of international linkages are found to be prevalent factors (even dominant over R&D).
Abstract The presence of lipid alterations in lipid rafts from the frontal cortex in late stages of Alzheimer's disease (AD) has been recently demonstrated. Here, we have isolated and analyzed the ...lipid composition of lipid rafts from different brain areas from control and AD subjects at initial neuropathologic stages. We have observed that frontal cortex lipid rafts are profoundly altered in AD brains from the earliest stages of AD, namely AD I/II. These changes in the lipid matrix of lipid rafts affected both lipid classes and fatty acids and were also detected in the entorhinal cortex, but not in the cerebellum from the same subjects. Paralleling these changes, lipid rafts from AD frontal and entorhinal cortices displayed higher anisotropy for environment-sensitive probes, indicating that lipid changes in AD lipid rafts increased membrane order and viscosity in these domains. The pathophysiological consequences of these alterations in the development and progression of AD were strengthened by the significant, and specific, accumulation of β-secretase within the lipid rafts of AD subjects even at the earliest stages. Our results provide a mechanistic connection between lipid alterations in these microdomains and amyloidogenic processing of amyloid precursor protein.
DHA (docosahexaenoic acid) is perhaps the most pleiotropic molecule in nerve cell biology. This long-chain highly unsaturated fatty acid has evolved to accomplish essential functions ranging from ...structural components allowing fast events in nerve cell membrane physiology to regulation of neurogenesis and synaptic function. Strikingly, the plethora of DHA effects has to take place within the hostile pro-oxidant environment of the brain parenchyma, which might suggest a molecular suicide. In order to circumvent this paradox, different molecular strategies have evolved during the evolution of brain cells to preserve DHA and to minimize the deleterious effects of its oxidation. In this context, DHA has emerged as a member of the “indirect antioxidants” family, the redox effects of which are not due to direct redox interactions with reactive species, but to modulation of gene expression within thioredoxin and glutathione antioxidant systems and related pathways. Weakening or deregulation of these self-protecting defenses orchestrated by DHA is associated with normal aging but also, more worryingly, with the development of neurodegenerative diseases. In the present review, we elaborate on the essential functions of DHA in the brain, including its role as indirect antioxidant, the selenium connection for proper antioxidant function and their changes during normal aging and in Alzheimer’s disease.
Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated ...fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.
The collaborative economy has become one of the fastest-growing areas since the great recession of 2008, with passenger transport activities being of particular importance. Based on on-demand ride ...services, in which passengers are connected with community drivers through a smartphone app, these collaborative transport activities are not all of a homogeneous nature, and need to be differentiated according to the type of service provided to understand the socioeconomic and environmental characteristics that determine their widespread use. The objective of this paper is to analyze the determinants of use of the two main online platforms for transport in Europe: Blablacar (ride-sharing) and Uber (ride-hailing), representing two different business models for shared mobility. Our contribution is an empirical analysis emphasizing the role of digital skills and employing a mixture analysis technique that permits the distinction between these two platforms models. Our results show that beyond their strong linkage to the digital environment, the determinants of using both platforms differ. In the case of Blablacar, the results show a closed user profile influenced by age, educational level, live as a couple or urban environment. However, the user profile for Uber is open and more diffuse, with a preference for female population.
•Hailing ride (UBER) and sharing ride (BLABLACAR) are different business models.•Digital skills and trust condition the use of both collaborative platforms.•Youth and higher education increase probability for using Blablacar.•Uber user profile is open with preference for women.
There exists considerable interest in the identification of molecular traits during early stages of Alzheimer's disease (AD). Mild cognitive impairment (MCI) is considered the closest prodromal stage ...of AD, and to develop gradually from earlier stages although not always progresses to AD. Classical cerebrospinal fluid (CSF) AD biomarkers, amyloid-β peptides and tau/p-tau proteins, have been measured in prodromal stages yet results are heterogeneous and far from conclusive. Therefore, there exists a pressing need to identify a neurochemical signature for prodromal stages and to predict which cases might progress to AD.
Exploring potential CSF biomarkers related to brain oxidative and inorganic biochemistry during prodromal stages of the disease.
We have analyzed CSF levels of lipoxidative markers (MDA and 8-isoF2α), biometals (Cu, Zn, Se, Mn, and Fe), iron-transport protein transferrin (TFER), antioxidant enzymes (SOD and GPx4), detoxifying enzymes (GST and BuChE), as well as classical amyloid-β and total and phosphorylated tau, in cognitively healthy controls, patients with MCI, and subjects exhibiting subjective memory complaints (SMC).
Inter-group differences for several variables exhibit differentiable trends along the HC ⟶ SMC ⟶ MCI sequence. More interestingly, the combination of Se, Cu, Zn, SOD, TFER, and GST variables allow differentiable fingerprints for control subjects and each prodromal stage. Further, multivariate scores correlate positively with neurocognitive In-Out test, hence with both episodic memory decline and prediction to dementia.
We conclude that changes in the CSF biochemistry related to brain oxidative defense and neurometallomics might provide more powerful and accurate diagnostic tools in preclinical stages of AD.
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