Alzheimer's disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of ...neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD.
AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease.
We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation.
Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.
The transatlantic transport of mineral dust from Africa is a persistent atmospheric phenomenon, clue for understanding the impacts of dust at the global scale. As part of the DUST Aging and Transport ...from Africa to the Caribbean (Dust‐ATTACk) intensive field campaign, the size distribution and optical properties of mineral dust were measured in June–July 2012 on the east coast of Puerto Rico, more than 5000 km from the west coast of Africa. During the recorded dust events, the PM10 (particulate matter 10 micrometers or less in diameter) concentrations increased from 20 to 70 µg m−3. Remote sensing observations and modeling analysis were used to identify the main source regions, which were found in the Western Sahara, Mauritania, Algeria, Niger, and Mali. The microphysical and optical properties of the dust plumes were almost independent of origin. The size distribution of mineral dust after long‐range transport may have modal diameters similar to those on the eastern side of the Atlantic short time after emission, possibly depending on height of transport. Additional submicron particles of anthropogenic absorbing aerosols (likely from regional marine traffic activities) can be mixed within the dust plumes, without affecting in a significant way the PM10 absorption properties of dust observed in Puerto Rico. The Dust‐ATTACk experimental data set may be useful for modeling the direct radiative effect of dust. For accurate representation of dust optical properties over the Atlantic remote marine region, we recommend mass extinction efficiency (MEE) and single‐scattering albedo values in the range 1.1–1.5 m2 g−1 and 0.97–0.98, respectively, for visible wavelengths.
Key Points
Microphysical and optical properties of mineral dust independent of origin after transport
Size distribution of mineral dust after long‐range transport may resemble to short range
Visible mass extinction efficiency and single‐scattering albedo around 1.1‐1.5 m2 g‐1 and 0.97‐0.98
During aging, changes in gene expression are associated with a decline in physical and cognitive abilities. Here, we investigate the connection between changes in mRNA and protein expression in the ...brain by comparing the transcriptome and proteome of the mouse cortex during aging. Our transcriptomic analysis revealed that aging mainly triggers gene activation in the cortex. We showed that an increase in mRNA expression correlates with protein expression, specifically in the anterior cingulate cortex, where we also observed an increase in cortical thickness during aging. Genes exhibiting an aging-dependent increase of mRNA and protein levels are involved in sensory perception and immune functions. Our proteomic analysis also identified changes in protein abundance in the aging cortex and highlighted a subset of proteins that were differentially enriched but exhibited stable mRNA levels during aging, implying the contribution of aging-related post- transcriptional and post-translational mechanisms. These specific genes were associated with general biological processes such as translation, ribosome assembly and protein degradation, and also important brain functions related to neuroplasticity. By decoupling mRNA and protein expression, we have thus characterized distinct subsets of genes that differentially adjust to cellular aging in the cerebral cortex.
We present a simultaneous approach to solve the integrated vehicle and crew scheduling problem in an extra urban context. We consider the single depot case with a heterogeneous fleet of vehicles. We ...propose a constraint based model which is subsequently solved by a Greedy Randomized Adaptive Search Procedure. The construction phase of each initial solution relies on constraint programming techniques, while the local search phase exploits a powerful neighborhood exploration mechanism. The computational experiments conducted on real-world instances show the effectiveness and the flexibility of the approach compared with the classical sequential vehicle and crew scheduling.
Accurate multiplicities of prompt fission neutrons emitted in neutron-induced fission on a large energy range are essential for fundamental and applied nuclear physics. Measuring them to high ...precision for radioactive fissioning nuclides remains, however, an experimental challenge. In this work, the average prompt-neutron multiplicity emitted in the 239Pu(n,f) reaction was extracted as a function of the incident-neutron energy, over the range 1-700 MeV, with a novel technique, which allowed to minimize and correct for the main sources of bias and thus achieve unprecedented precision.At low energies, our data validate for the first time the ENDF/B-VIII.0 nuclear data evaluation with an independent measurement and reduce the evaluated uncertainty by up to 60%. This work opens up the possibility of precisely measuring prompt fission neutron multiplicities on highly radioactive nuclei relevant for an essential component of energy production world-wide.
Air pollution in Chinese megacities has reached extremely hazardous levels, and human activities are responsible for the emission or production of large amounts of particulate matter (PM). In ...addition to PM from anthropogenic sources, natural phenomena, such as dust storms over Asian deserts, may also emit large amounts of PM, which lead episodically to poor air quality over Chinese megacities. In this paper, we quantify the degradation of air quality by dust over Beijing, Chengdu and Shanghai megacities using the three dimensions (3D) chemistry transport model CHIMERE, which simulates dust emission and transport online. In the first part of our work, we evaluate dust emissions using Moderate Resolution Imaging Spectroradiometer (MODIS) and Infrared Atmospheric Sounding Interferometer (IASI) satellite observations of aerosol optical depth, respectively, in the visible and the thermal infrared over source areas. PM simulations were also evaluated compared to surface monitoring stations. Then, mineral dust emissions and their impacts on particle composition of several Chinese megacities were analyzed. Dust emissions and transport over China were simulated during three years (2011, 2013 and 2015). Annual dust contributions to the PM 10 budget over Beijing, Chengdu and Shanghai were evaluated respectively as 6.6%, 9.5% and 9.3%. Dust outbreaks largely contribute to poor air quality events during springtime. Indeed it was found that dust significantly contribute for 22%, 52% and 43% of spring PM 10 events (for Beijing, Chengdu and Shanghai respectively).
Two weeks of high-frequency radar measurements collected at the Alderney Race are compared with the results of a three-dimensional fully coupled wave–current model. Spatial current measurements are ...rare in this site, otherwise well investigated through modelling. Thus, the radar measurements offer a unique opportunity to examine the spatial reliability of numerical results, and can help to improve our understanding of the complex currents in the area. Comparison of observed and modelled surface current velocities showed a good agreement between the methods, represented by root mean squared errors ranging from 14 to 40 cm s
−1
and from 18 to 60 cm s
−1
during neap and spring tides, respectively. Maximum errors were found in shallow regions with consistently high current velocities, represented by mean neap and spring magnitudes of 1.25 m s
−1
and 2.7 m s
−1
, respectively. Part of the differences between modelled and observed surface currents in these areas are thought to derive from limitations in the k-epsilon turbulence model used to simulate vertical mixing, when the horizontal turbulent transport is high. In addition, radar radial currents showed increased variance over the same regions, and might also be contributing to the discrepancies found. Correlation analyses yielded magnitudes above 0.95 over the entire study area, with better agreement during spring than during neap tides, probably because of an increase in the phase lag between radar and model velocities during the latter.
This article is part of the theme issue ‘New insights on tidal dynamics and tidal energy harvesting in the Alderney Race’.
We present the first direct evidence that the hygroscopic properties of super micron (>1 µm) African dust particles did not change despite undergoing long‐range transport across the Atlantic toward ...the Caribbean. Concurrent measurements of chemical composition show that most of mineral dust was chemically unprocessed and externally mixed. A minor portion of mineral dust was internally mixed with sulfate and chloride (~13–24% by number) or aggregated with sea‐salt particles (~3–6%). Only dust particles aggregated with sea salt showed significant hygroscopic growth above 75% relative humidity (RH), resulting in a decrease in extinction mass efficiency by up to a factor 2.2. All other dust particles did not take up significant amounts of water when exposed to up to 94% RH. These results demonstrate that the direct radiative effect of African dust in this region remained independent of RH and an external mixing state could be considered for evaluating the climate effects of dust.
Key Points
First direct measurements of hygroscopic properties of dust in the Caribbean
Dust remained chemically unprocessed and nonhygroscopic despite their long‐range transport
Direct radiative effect of dust was largely independent of RH
For several decades, an increase in disease or pest emergences due to anthropogenic introduction or environmental changes has been recorded. This increase leads to serious threats to the genetic and ...species diversity of numerous ecosystems. Many of these events involve species with poor or no genomic resources (called here "orphan species"). This lack of resources is a serious limitation to our understanding of the origin of emergent populations, their ability to adapt to new environments and to predict future consequences to biodiversity. Analyses of genetic diversity are an efficient method to obtain this information rapidly, but require available polymorphic genetic markers.
We developed a generic bioinformatics pipeline to rapidly isolate such markers with the goal for the pipeline to be applied in studies of invasive taxa from different taxonomic groups, with a special focus on forest fungal pathogens and insect pests. This pipeline is based on: 1) an automated de novo genome assembly obtained from shotgun whole genome sequencing using paired-end Illumina technology; 2) the isolation of single-copy genes conserved in species related to the studied emergent organisms; 3) primer development for multiplexed short sequences obtained from these conserved genes. Previous studies have shown that intronic regions of these conserved genes generally contain several single nucleotide polymorphisms within species. The pipeline's functionality was evaluated with sequenced genomes of five invasive or expanding pathogen and pest species in Europe (
(Romagn.) Herink 1973,
Steiner & Buhrer 1934,
(fr.) Dicko & B. Sutton 1980,
(Griffon & Maubl.) U. Braun & S. Takam. 2000,
Denis & Schiffermüller, 1775). We successfully isolated several pools of one hundred short gene regions for each assembled genome, which can be amplified in multiplex. The bioinformatics pipeline is user-friendly and requires little computational resources. This easy-to-set-up and run method for genetic marker identification will be useful for numerous laboratories studying biological invasions, but with limited resources and expertise in bioinformatics.
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