A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

N′-(3,5-Dichloro-2-hy­droxy­benzyl­idene)-4-(dimethyl­amino)­benzohydrazide methanol monosolvate

The title compound, C16H15Cl2N3O2·CH3OH, a Schiff base molecule, is prepared by the reaction of 3,5-dichloro­salicyl­aldehyde with 4-dimethyl­amino­benzohydrazide in methanol. The Schiff base mol­ecule is approximately planar, with a mean deviation from the least-squares plane defined by the non-H atoms of 0.0452 (3) Å, and with a dihedral angle between the benzene rings of 4.2 (3)°. This planarity is assisted by the formation of an intra­molecular O—H⋯N hydrogen bond. In the crystal, adjacent Schiff base mol­ecules are linked by two methanol mol­ecules through N—H⋯O and O—H⋯O hydrogen bonds, forming dimers

A new molecular model for water adsorption on graphitized carbon black

Adsorption of water on graphitized carbon black at various temperatures has been studied with a new molecular model of graphitized carbon black using Monte Carlo simulation. The model is a collection of graphene layers, modelled by the Steele potential, and a number of phenol groups forming clusters of various sizes which are placed randomly at the graphene edge sites to give an O/C ratio of 0.006. The results are compared with experimental data reported by Kiselev et al. [1] in 1968 for a range of temperatures, and for the first time a reconciliation between the experimental data and simulation has been successfully achieved. The simulation results show that water adsorbs preferentially around the functional groups to form clusters, which then grow and merge at the edges of the graphene layers, rather than adsorbing onto the basal planes of the graphene because the electrostatic interactions (hydrogen bonding) between water molecules are stronger than the basal plane-water dispersion interactions

Enantioselective nickel-catalyzed intramolecular allylic alkenylations enabled by reversible alkenylnickel E/Z isomerization

Enantioselective nickel-catalyzed arylative cyclizations of substrates containing a Z-allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza- and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions

Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow

An optical flow gradient algorithm was applied to spontaneously forming net- works of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e. a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling pat- terns. We begin by briefly reviewing the mathematics of the optical flow algorithm, and then describe how to solve for the displacement vectors and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the algorithm for capturing different types of spatiotemporal calcium activity. We discuss the imaging requirements, parameter selection and threshold selection for reliable measurements, and offer perspectives on uses of the vector data.Comment: 23 pages, 5 figures. Peer reviewed accepted version in press in Annals of Biomedical Engineerin

The Molecular Outflows in the rho Ophiuchi Main Cloud: Implications For Turbulence Generation

We present the results of CO (J=3-2) and CO (J=1-0) mapping observations toward the active cluster forming clump, L1688, in the rho Ophiuchi molecular cloud. From the CO (J=3-2) and CO (J=1-0) data cubes, we identify five outflows, whose driving sources are VLA 1623, EL 32, LFAM 26, EL 29, and IRS 44. Among the identified outflows, the most luminous outflow is the one from the prototypical Class 0 source, VLA 1623. We also discover that the EL 32 outflow located in the Oph B2 region has very extended blueshifted and redshifted lobes with wide opening angles. This outflow is most massive and have the largest momentum among the identified outflows in the CO (J=1-0) map. We estimate the total energy injection rate due to the molecular outflows identified by the present and previous studies to be about 0.2 L_solar, larger than or at least comparable to the turbulence dissipation rate [~(0.03 - 0.1) L_solar]. Therefore, we conclude that the protostellar outflows are likely to play a significant role in replenishing the supersonic turbulence in this clump.Comment: 37 pages, 9 figures, accepted for publication in The Astrophysical Journa

A Chandra Observation of the Obscured Star-Forming Complex W40

The young stellar cluster illuminating the W40 H II region, one of the nearest massive star forming regions, has been observed with the ACIS detector on board the Chandra X-ray Observatory. Due to its high obscuration, this is a poorly-studied stellar cluster with only a handful of bright stars visible in the optical band, including three OB stars identified as primary excitation sources. We detect 225 X-ray sources, of which 85% are confidently identified as young stellar members of the region. Two potential distances of the cluster, 260 pc and 600 pc, are used in the paper. Supposing the X-ray luminosity function to be universal, it supports a 600 pc distance as a lower limit for W40 and a total population of at least 600 stars down to 0.1 Mo under the assumption of a coeval population with a uniform obscuration. In fact, there is strong spatial variation in Ks-band-excess disk fraction and non-uniform obscuration due to a dust lane that is identified in absorption in optical, infrared and X-ray. The dust lane is likely part of a ring of material which includes the molecular core within W40. In contrast to the likely ongoing star formation in the dust lane, the molecular core is inactive. The star cluster has a spherical morphology, an isothermal sphere density profile, and mass segregation down to 1.5 Mo. However, other cluster properties, including a \leq{1} Myr age estimate and ongoing star formation, indicate that the cluster is not dynamically relaxed. X-ray diffuse emission and a powerful flare from a young stellar object are also reported.Comment: Accepted for publication in The Astrophysical Journal. 60 pages, 16 figure