Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease

The pathophysiology of sporadic Alzheimer\u27s disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD

Origin and distribution of terrestrial organic matter in the NW Mediterranean (Gulf of Lions): Exploring the newly developed BIT index

The Branched and Isoprenoid Tetraether (BIT) index is based on the relative abundance of nonisoprenoidal glycerol dialkyl glycerol tetraethers (GDGTs) derived from organisms living in terrestrial environments versus a structurally related isoprenoid GDGT ‘‘crenarchaeol’’ produced by marine Crenarchaeota. The BIT index varies between 0 and 1, representing marine and terrestrial organic matter (OM) end-members, respectively (Hopmans et al., Earth Planet. Sci. Lett., 224, 107–116, 2004). In this study, the applicability of the BIT index to trace terrestrial OM is tested in combination with other organic parameters (TOC, C/N ratio, δ13Corg, total lipid, and n-alkane) in the Gulf of Lions, a river-dominated continental margin of the western Mediterranean. We analyzed a variety of soils and riverbed sediments from the continent as well as surface sediments from the shelf and canyons. The BIT index in soils and riverbed sediments shows high values (>0.9), while it varies between 0.02 and 0.83 in marine sediments, decreasing seaward from the inner shelf to the slope. For marine surface sediments, high BIT values are associated with lower δ13Corg values as well as higher TOC contents and higher n-alkane concentrations. Our results confirm that the BIT index can be applied in coastal marine environments in order to characterize terrestrial OM as proposed by Hopmans et al. (2004). Therefore the BIT index is a useful addition to the proxies presently available for studying the origin and distribution of OM in continental margins and especially valuable in multiproxy studies

Transport and depositional process of soil organic matter during wet and dry storms on the Têt inner shelf (NW Mediterranean)

11 pages, 7 figuresRiver floods and storm waves are major processes for the dispersal and deposition of terrestrial organic matter (OM) in river-dominated coastal areas. A "wet storm" is connected to a flood with a high river discharge, while a "dry storm" is not associated with a flood. To better understand the sedimentation dynamics of terrestrial OM, especially soil OM, at the land-ocean interface during wet and dry storms, we studied sediment trap and core material collected on the Têt inner shelf (NW Mediterranean) using multiple organic proxies in combination with hydrodynamic parameters. The proportion of soil OM to the total OM in the trap material calculated based on the BIT (Branched and Isoprenoid Tetraether) index was higher during both wet (~ 40%) and dry (~ 30%) storms than during non-storm periods (~ 10%). However, only surface sediments (1-cm thick layers) recovered after December wet and moderate storms in 2003 showed enhanced soil OM percentages compared to the deeper sediments deposited during the last century. Given that the wet storm eroded 4-cm of seabed at the study site, flood-induced fresh soil OM was not deposited on the Têt inner shelf during the wet storm. However, the following moderate storm caused resuspension of flood-associated soil OM which was previously trapped nearshore. Accordingly soil OM was transported to the Têt inner shelf and stored there until the dry storm occurred. © 2008 Elsevier B.V. All rights reservedThis study was supported by a Marie Curie Intra-European Fellowship grant to J.-H. Kimand the EUROSTRATAFORMproject funded by the European UnionPeer Reviewe

Examining the provenance of branched GDGTs in the Tagus River drainage basin and its outflow into the Atlantic Ocean over the Holocene to determine their usefulness for paleoclimate applications

The distributions of branched glycerol dialkyl glycerol tetraethers (brGDGTs), which are transported from the soils where they are predominantly produced to marine sediments via rivers, have been applied in reconstructing mean annual air temperature (MAT) and pH of soils. However, paleoclimate reconstructions using sedimentary brGDGTs have proven difficult in arid regions, including the Iberian Peninsula. Recently, six novel 6-methyl brGDGTs have been described using new analytical methods (in addition to the nine 5-methyl brGDGTs previously used for climate reconstructions), and so new pH and MAT calibrations have been developed that were shown to improve the accuracy of reconstructions in a set of global soil samples, especially in arid regions. Because of this we decided to apply the new method to separate the 5- and 6-methyl isomers along with the novel calibrations to a sample set from the Iberian Peninsula to determine whether it improves paleoclimate reconstructions in this area. This set includes samples that run in a transect from source to sink along the Tagus River and out to the deep ocean off the Portuguese margin spanning the last 6000 years. We found that although pH reconstructions in the soils were improved using the new calibration, MAT reconstructions were not much better even with the separation of the 5- and 6-methyl brGDGTs. This confirmed the conclusion of previous studies that the amount of aquatically produced brGDGTs is overwhelming the soil-derived ones in marine sediments and complicating MAT reconstructions in the region. Additionally, the new separation revealed a strong and until now unseen relationship between the new degree of cyclization (DC') of the brGDGTs and MAT that could be making temperature reconstructions in this and other arid regions difficult

Examining the provenance of branched GDGTs in the Tagus River drainage basin and its outflow into the Atlantic Ocean over the Holocene to determine their usefulness for paleoclimate applications

The distributions of branched glycerol dialkyl glycerol tetraethers (brGDGTs), which are transported from the soils where they are predominantly produced to marine sediments via rivers, have been applied in reconstructing mean annual air temperature (MAT) and pH of soils. However, paleoclimate reconstructions using sedimentary brGDGTs have proven difficult in arid regions, including the Iberian Peninsula. Recently, six novel 6-methyl brGDGTs have been described using new analytical methods (in addition to the nine 5-methyl brGDGTs previously used for climate reconstructions), and so new pH and MAT calibrations have been developed that were shown to improve the accuracy of reconstructions in a set of global soil samples, especially in arid regions. Because of this we decided to apply the new method to separate the 5- and 6-methyl isomers along with the novel calibrations to a sample set from the Iberian Peninsula to determine whether it improves paleoclimate reconstructions in this area. This set includes samples that run in a transect from source to sink along the Tagus River and out to the deep ocean off the Portuguese margin spanning the last 6000 years. We found that although pH reconstructions in the soils were improved using the new calibration, MAT reconstructions were not much better even with the separation of the 5- and 6-methyl brGDGTs. This confirmed the conclusion of previous studies that the amount of aquatically produced brGDGTs is overwhelming the soil-derived ones in marine sediments and complicating MAT reconstructions in the region. Additionally, the new separation revealed a strong and until now unseen relationship between the new degree of cyclization (DC') of the brGDGTs and MAT that could be making temperature reconstructions in this and other arid regions difficul