Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles.

Hepatic sinusoidal endothelial cells are unique among endothelial cells in their ability to internalize and process a diverse range of antigens. DC-SIGNR, a type 2 C-type lectin expressed on liver sinusoids, has been shown to bind with high affinity to hepatitis C virus (HCV) E2 glycoprotein. DC-SIGN is a closely related homologue reported to be expressed only on dendritic cells and a subset of macrophages and has similar binding affinity to HCV E2 glycoprotein. These receptors function as adhesion and antigen presentation molecules. We report distinct patterns of DC-SIGNR and DC-SIGN expression in human liver tissue and show for the first time that both C-type lectins are expressed on sinusoidal endothelial cells. We confirmed that these receptors are functional by demonstrating their ability to bind HCV E2 glycoproteins. Although these lectins on primary sinusoidal cells support HCV E2 binding, they are unable to support HCV entry. These data support a model where DC-SIGN and DC-SIGNR on sinusoidal endothelium provide a mechanism for high affinity binding of circulating HCV within the liver sinusoids allowing subsequent transfer of the virus to underlying hepatocytes, in a manner analogous to DC-SIGN presentation of human immunodeficiency virus on dendritic cells

Improved seasonal prediction of European summer temperatures with new five-layer soil-hydrology scheme

We evaluate the impact of a new 5-layer soil-hydrology scheme on seasonal hindcast skill of 2-meter temperatures over Europe obtained with the Max Planck Institute Earth System Model (MPI-ESM). Assimilation experiments from 1981 to 2010 and 10-member seasonal hindcasts initialized on 1 May each year are performed with MPI-ESM in two soil configurations, one using a bucket scheme and one a new 5-layer soil-hydrology scheme. We find the seasonal hindcast skill for European summer temperatures to improve with the 5-layer scheme compared to the bucket scheme, and investigate possible causes for these improvements. First, improved indirect soil moisture assimilation allows for enhanced soil moisture-temperature feedbacks in the hindcasts. Additionally, this leads to improved prediction of anomalies in the 500 hPa geopotential height surface, reflecting more realistic atmospheric circulation patterns over Europe

Thermal and ultraviolet-visible light stability kinetics of co-nanoencapsulated carotenoids.

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Visualizing brain inflammation with a shingled-leg radio-frequency head probe for (19)F/(1)H MRI

Magnetic resonance imaging (MRI) provides the opportunity of tracking cells in vivo. Major challenges in dissecting cells from the recipient tissue and signal sensitivity constraints albeit exist. In this study, we aimed to tackle these limitations in order to study inflammation in autoimmune encephalomyelitis. We constructed a very small dual-tunable radio frequency (RF) birdcage probe tailored for (19)F (fluorine) and (1)H (proton) MR mouse neuroimaging. The novel design eliminated the need for extra electrical components on the probe structure and afforded a uniform -field as well as good SNR. We employed fluorescently-tagged (19)F nanoparticles and could study the dynamics of inflammatory cells between CNS and lymphatic system during development of encephalomyelitis, even within regions of the brain that are otherwise not easily visualized by conventional probes. (19)F/(1)H MR Neuroimaging will allow us to study the nature of immune cell infiltration during brain inflammation over an extensive period of time

Discovery of Ircinianin Lactones B and C: two new cyclic sesterterpenes from the marine sponge Ircinia wistarii

Two new ircinianin-type sesterterpenoids, ircinianin lactone B and ircinianin lactone C (7 and 8), together with five known entities from the ircinianin compound family (1, 3-6) were isolated from the marine sponge Ircinia wistarii. Ircinianin lactones B and C (7 and 8) represent new ircinianin terpenoids with a modified oxidation pattern. Despite their labile nature, the structures could be established using a combination of spectroscopic data, including HRESIMS and 1D/2D NMR techniques, as well as computational chemistry and quantum-mechanical calculations. In a broad screening approach for biological activity, the class-defining compound ircinianin (1) showed moderate antiprotozoal activity against Plasmodium falciparum (IC50 25.4 μM) and Leishmania donovani (IC50 16.6 μM)

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

A higher-resolution version of the Max Planck Institute Earth System Model (MPI-ESM1.2-HR)

The MPI‐ESM1.2 is the latest version of the Max Planck Institute Earth System Model and is the baseline for the Coupled Model Intercomparison Project Phase 6 and current seasonal and decadal climate predictions. This paper evaluates a coupled higher‐resolution version (MPI‐ESM1.2‐HR) in comparison with its lower‐resolved version (MPI‐ESM1.2‐LR). We focus on basic oceanic and atmospheric mean states and selected modes of variability, the El Niño/Southern Oscillation and the North Atlantic Oscillation. The increase in atmospheric resolution in MPI‐ESM1.2‐HR reduces the biases of upper‐level zonal wind and atmospheric jet stream position in the northern extratropics. This results in a decrease of the storm track bias over the northern North Atlantic, for both winter and summer season. The blocking frequency over the European region is improved in summer, and North Atlantic Oscillation and related storm track variations improve in winter. Stable Atlantic meridional overturning circulations are found with magnitudes of ~16 Sv for MPI‐ESM1.2‐HR and ~20 Sv for MPI‐ESM1.2‐LR at 26°N. A strong sea surface temperature bias of ~5°C along with a too zonal North Atlantic current is present in both versions. The sea surface temperature bias in the eastern tropical Atlantic is reduced by ~1°C due to higher‐resolved orography in MPI‐ESM‐HR, and the region of the cold‐tongue bias is reduced in the tropical Pacific. MPI‐ESM1.2‐HR has a well‐balanced radiation budget and its climate sensitivity is explicitly tuned to 3 K. Although the obtained reductions in long‐standing biases are modest, the improvements in atmospheric dynamics make this model well suited for prediction and impact studies

Comparison between non‐orographic gravity‐wave parameterizations used in QBOi models and Strateole 2 constant‐level balloons

Gravity‐wave (GW) parameterizations from 12 general circulation models (GCMs) participating in the Quasi‐Biennial Oscillation initiative (QBOi) are compared with Strateole 2 balloon observations made in the tropical lower stratosphere from November 2019–February 2020 (phase 1) and from October 2021–January 2022 (phase 2). The parameterizations employ the three standard techniques used in GCMs to represent subgrid‐scale non‐orographic GWs, namely the two globally spectral techniques developed by Warner and McIntyre (1999) and Hines (1997), as well as the “multiwaves” approaches following the work of Lindzen (1981). The input meteorological fields necessary to run the parameterizations offline are extracted from the ERA5 reanalysis and correspond to the meteorological conditions found underneath the balloons. In general, there is fair agreement between amplitudes derived from measurements for waves with periods less than 1 $$1$$ h and parameterizations. The correlation between the daily observations and the corresponding results of the parameterization can be around 0.4, which is 99 % $$99\%$$ significant, since 1200 days of observations are used. Given that the parameterizations have only been tuned to produce a quasi‐biennial oscillation (QBO) in the models, the 0.4 correlation coefficient of the GW momentum fluxes is surprisingly good. These correlations nevertheless vary between schemes and depend little on their formulation (globally spectral versus multiwaves for instance). We therefore attribute these correlations to dynamical filtering, which all schemes take into account, whereas only a few relate the gravity waves to their sources. Statistically significant correlations are mostly found for eastward‐propagating waves, which may be due to the fact that during both Strateole 2 phases the QBO is easterly at the altitude of the balloon flights. We also found that the probability density functions (pdfs) of the momentum fluxes are represented better in spectral schemes with constant sources than in schemes (“spectral” or “multiwaves”) that relate GWs only to their convective sources